Application of Circulating Tumor DNA in Precision Diagnosis and Treatment of Colorectal Cancer / 肿瘤防治研究

Colorectal cancer (CRC) is one of the most common malignant tumors recorded worldwide. This condition has high morbidity and mortality and seriously endangers people's health. Traditional diagnostic models fail to meet people's current needs for real-time monitoring of tumors. Compared with traditional detection methods, ctDNA detection is not only noninvasive but can also attain real-time detection of comprehensive genomic information of tumors. The advancement of detection technology has gradually highlighted the potential of ctDNA detection in the clinical treatment of CRC. This article reviews the advancements on the clinical application of ctDNA in early screening, minimal residual disease detection, and guidance on individualized treatment of CRC patients.

Inhibition of ANGPT2 activates autophagy during hypertrophic scar formation via PI3K/AKT/mTOR pathway

Abstract Background Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. Objective This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. Methods RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. Results ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. Study limitations The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. Conclusions ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS.

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Abstract Objective To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design A retrospective single-institution cohort study. Patients The perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors' institution between November 2012 and June 2019 were retrospectively analyzed. Methods The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations The number of enrolled patients was relatively small and patients' treatment options varied. Conclusions A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target.

Association of depressive symptoms, Internet addiction and insomnia among medical students in Anhui Province / 中国学校卫生

Objective@#To investigate the status of insomnia, Internet addiction, and depressive symptoms among medical students and to analyze the effect of Internet addiction on insomnia and the mediating role of depressive symptoms, in order to provide a basis for the development of targeted interventions and measurements for medical students.@*Methods@#A stratified whole group sampling method was used to select full-time college students from three medical universities in Anhui Province. The Chinese version of Insomnia Severity Index (ISI), Internet Addiction Test (IAT) scale and 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate the symptoms of insomnia, Internet addiction and depressive in students. A multivariate Logistic regression analysis was used to explore the factors influencing insomnia among medical students and to analyze the relationship between insomnia with Internet addiction and depressive symptoms, respectively.@*Results@#The overall rate of Internet addiction was 49.5%, depressive symptoms was 39.5%, insomnia was 18.6%. High academic stress, and the presence of surrounding people diagnosed with COVID-19 were associated with a higher risk of insomnia ( P <0.05). The higher the level of Internet addiction (mild, OR =2.60; moderate/severe, OR =4.21) and depression. (mild, OR =6.35; moderate/severe, OR =19.32), the higher the risk of insomnia. Mediated effect analysis showed that Internet addiction had a direct predictive effect ( β =0.02, P <0.05) on insomnia and also indirectly affected insomnia through depression (indirect effect=0.07，95% CI =0.06-0.08).@*Conclusion@#The detected rates of insomnia, Internet addiction and depressive symptoms are high among medical students in Anhui Province, and Internet addiction and depressive symptoms are risk factors for insomnia, which should be given more attention and appropriate interventions when necessary to improve their physical and mental health.

L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma

Abstract Objectives Accurate prognosis assessment across the heterogeneous population of brain metastases is very important, which may facilitate clinical decision-making and appropriate stratification of future clinical trials. Previous studies have shown the L1 Cell Adhesion Molecule (L1CAM) is potentially involved in human malignancies of multiple different samples and unfavorable survival. However, no data of L1CAM are available for the brain metastases from lung adenocarcinoma, especially for the one with neurosurgical resection. Method The authors investigated the L1CAM expression in cranial metastatic lesions for patients with brain metastases from lung adenocarcinoma after neurosurgical resection using tissue microarrays that were obtained from the Department of Neurosurgery at the Cancer Hospital of the Chinese Academy of Medical Sciences. Furthermore, the relationship between L1CAM expression and clinic-pathological parameters, including overall survival time, was analyzed to assess the prognostic value of L1CAM. Results L1CAM high expression was found in 62.30% of brain metastases from lung adenocarcinoma and significantly correlated with brain metastasis number (p = 0.028) and Lung-molGPA score (p = 0.042). Moreover, L1CAM expression was an independent predictor of survival for brain metastases after neurosurgical resection in a multivariate analysis. Patients with L1CAM high expression had unfavorable overall survival time (p = 0.016). In addition, the multivariate analysis also showed age and extracranial transfer were also the independent prognostic factors for this type of patient with brain metastases. Conclusions A subset of brain metastases from lung adenocarcinoma aberrantly expresses L1CAM. L1CAM is a novel independent prognostic factor for brain metastasis from lung adenocarcinoma after neurosurgical resection.

Research progress in prevention and treatment of diabetic retinopathy by simplex and compounds of Chinese materia medica / 中国药理学与毒理学杂志

Diabetic retinopathy (DR) is a common microvascular complication of diabetes. It has become the main cause of adult blindness. Recent studies show that traditional Chinese materia medica (TCMM) and compounds can help the prevention and treatment of DR. The mechanism may be attributed to protection of retinal pericytes, endothelial cells and retinal neurodegeneration, reduction of advanced glycation end products (AGEs), receptor of AGEs (RAGE), vascular endothelial growth factor (VEGF) expression, inhibition of nuclear factor-kappaB (NF-ΚB) activation, alleviation of mitochondrial oxidative stress, and inhibition of apoptosis. In this paper, we review the recent laboratory findings of DR treated with TCMM and compounds in order to provide reference for the prevention of DR and for TCMM innovation.

Trend analysis of morbidity and mortality of colorectal cancer in China from 1988 to 2009 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the trend change of the morbidity and mortality of colorectal cancer in China in order to provide reference to the prevention and control of colorectal cancer.</p><p><b>METHODS</b>According to the 1-3 volumes of "Pathogenesis and death of malignancies in pilot program city and county of China", "Pathogenesis and death of cancer in China"(2003-2007) and "Registration annual report of tumor in China" published in 2011 and 2012, data of pathogenesis and death of colorectal cancer from 10 tumor registration spots, including Beijing urban, Shanghai urban, Wuhan urban, Harbin urban (defined as city urban), and Hebei Ci County, Jiangsu Qidong District, Zhejiang Jiashan District, Guangxi Fusui County, Fujian Changle District, Henan Lin County (defined as rural district), between 1988 and 2009 were collected. The morbidity and mortality were elucidated with world population standardized rate. Ratio of pathogenesis to death was calculated with crude rate of morbidity and mortality. Data of 22 years were enrolled into the linear regression analysis to calculate the annual change rate of morbidity and mortality statistically.</p><p><b>RESULTS</b>(1) Colon cancer: morbidity presented increasing trend; male morbidity in city urban increased faster; mortality presented increasing trend as well; no significant difference of increasing velocity was observed between city urban and rural district; morbidity and mortality in city urban were higher compared to rural district; morbidity and mortality of males were higher compared to females; except stable Fujian Changle District, ratio of pathogenesis to death presented decreased trend in Shanghai urban and Hebei Ci County, and increased trend in other 7 spots (all P<0.05). (2) Rectal cancer: morbidity presented increasing trend, and its increasing velocity of city urban was faster compared to rural district; mortality presented decreased trend, especially in females, and this trend in rural district was worse compared to city urban; morbidity and mortality of males were higher compared to females, while no significant difference was observed between city urban and rural district; morbidity and mortality of males and females in Zhejiang Jiashan District were all decreased (all P<0.05); except stable Harbin city, ratio of pathogenesis to death presented increased trend in other 9 spots (all P<0.05). (3) Ratio analysis of morbidity and mortality showed that percentage of colon cancer increased gradually in all 10 spots between 1988-2009.</p><p><b>CONCLUSIONS</b>In the past 2 decades, the overall morbidity and mortality of colorectal cancer are higher in city urban and in male as compared with rural district and female. Colon cancer has higher morbidity than rectal cancer and its morbidity and mortality present increased trend, while morbidity of rectal cancer presents increased trend but its mortality presents decreased trend.</p>

Efficacy and safety of cyclophosphamide as a sequential immunotherapy drug for anti-N-methyl-D-aspartate receptor encephalitis in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cyclophosphamide as a second-line drug in the treatment of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.</p><p><b>METHODS</b>Six children with anti-NMDAR encephalitis, who showed poor response to steroids and intravenous immunoglobulin, were given cyclophosphamide as a second-line immunotherapy. Follow-up was performed to evaluate the efficacy and safety of cyclophosphamide.</p><p><b>RESULTS</b>After first-line immunotherapy for 1-4 weeks, the six patients had reduced psychiatric symptoms, seizures, and involuntary movements; three patients had an improved level of consciousness and were able to make simple conversations. However, all the patients still showed slow response, as well as cortical dysfunction symptoms such as aphasia, alexia, agraphia, acalculia, apraxia, and movement disorders. The six patients continued to receive cyclophosphamide as a sequential therapy. They were able to answer simple questions 7 days after treatment. Three school-aged patients were able to make simple calculation, had greatly improved reading and writing ability, and almost recovered self-care ability 2-3 weeks later. The cognitive function of the six patients was almost restored to the level before the onset of disease, and their living ability returned to normal 2-3 months later. During the treatment period, there were no adverse reactions or abnormal results of routine blood test and liver and kidney function tests.</p><p><b>CONCLUSIONS</b>Children with anti-NMDAR encephalitis should be given appropriate immunotherapy as soon as possible. Cyclophosphamide as a sequential therapy has good efficacy and safety.</p>

Inhibitory effect of miR-20b on airway inflammation in asthmatic mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of miR-20b in inhibiting airway inflammation in a mouse model of asthma.</p><p><b>METHODS</b>Female BALB/c mouse models of asthma, established by sensitizing and challenging the mice with a mixture of ovalbumin and aluminum hydroxide, were subjected to intranasal instillation of 20 µg miR-20b mimics or a miR-20b scramble every 3 days. On day 49, bronchoalveolar lavage fluid (BALF) was collected from the mice to examine the counts of total cells and different cell populations; HE staining was used to observe the pathological changes of the lung tissue, and the concentration of vascular endothelial growth factor (VEGF) in BALF was detected by ELISA.</p><p><b>RESULTS</b>Treatment of the asthmatic mice with miR-20b mimics decreased not only the counts of the total leukocytes, neutrophils and eosinophils in the BALF but also mucus secretion in the airway and inflammatory cell infiltration around the bronchus, and lessened thickening of the airway mucosa. Instillation with miR-20b mimics significantly reduced the concentration of VEGF in BALF from 28.55±3.42 pg/mL in the asthma model group to 18.19±3.67 pg/mL (P<0.01).</p><p><b>CONCLUSION</b>MiR-20b can inhibit airway inflammation in asthmatic mice possibly by reducing the expression of VEGF.</p>

Frequency of different subtypes of spinocerebellar ataxia in the Han nationality of Hunan province in China / 中南大学学报(医学版)

OBJECTIVE@#To determine the frequency of different subtypes of spinocerebellar ataxias (SCAs) in the Han nationality of Hunan province in China.@*METHODS@#The mutations of SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, and dentatorulral-pallidoluysian (DRPLA) were detected with the polymerase chain reaction (PCR), denaturing polyacrylamide gel and DNA sequencing techniques in 139 autosomal dominant SCA families and 61 sporadic SCA patients.@*RESULTS@#Of the 139 families, 11 (7.9%) were positive for SCA1, 9(6.5%) were positive for SCA2, 71 (51.1%) were positive for SCA3, 4 (2.9%) were positive for SCA6, 2 (1.4%) were positive for SCA7, and none was positive for SCA17 and DRPLA. There was 1 SCA2 patient, 3 SCA3 patients, 1 SCA6 patient in the 61 sporadic SCA patients.@*CONCLUSION@#The frequency of SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA patients in the Han nationality of Hunan province. SCA6 and SCA7 are rare subtypes.

Mycobacterium tuberculosis antigen activates the nuclear factor-?B pathway and delays spontaneous apoptosis in neutrophils / 中华检验医学杂志

Objective To explore the effect of Mycobacterium tuberculosis antigen (Mtb-Ag) on neutrophils apoptosis.Methods The fresh isolated neutrophils from healthy adults blood were cultured with Mtb-Ag for 24 h,with or without pretreatment of nuclear factor -?B (NF-?B) inhibitor N-tosyl-L-phenylanyl chloromethyl ketone (TPCK) for 30 minutes.Annexin V staining and Flow cytometry were used to measure cell apoptosis of neutrophils.NF-?B DNA binding was measured by gelelectrophorestic mobility shift assay (EMSA) in neutrophils after incubated with Mtb-Ag for 0,1,2,4,6,24 hours.Results Comparing to the spontaneous apoptosis (55%?6%) of neutrophils after culture in vitro for 24 h,treatment of Mtb-Ag (1.125 mg/ml) decreased the cell apoptosis of neutrophils (32%?3%).The NF-?B shift bands were detected at 1 h in neutrophils after stimulated by Mtb-Ag,and reached maximum peak at 2 hours,and then returned to basal levels within 24 h.Pretreatment of TPCK inhibited the anti-apoptosis role of Mtb-Ag in neutrophils.Conclusion Mtb-Ag prevents neutrophils apoptosis and its inhibitory role concerns NF-?B pathway.