Establishment and validation of clinical prediction model for steroid-resistant nephrotic syndrome in children / 中华儿科杂志

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ2=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ2=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.

Biomarkers and Target Mechanisms of Epimedii Folium Intervention on Breast Cancer Stem Cells Based on Chip Analysis and Network Pharmacology / 中国实验方剂学杂志

Objective:To elucidate the potential molecular markers and drug-compound-target mechanism of Epimedii Folium intervention on breast cancer stem cells（BCSCs） through chip analysis combined with network pharmacology and experimental validation. Method:Relevant drug information was retrieved in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） to obtain the active components and potential targets of Epimedii Folium. "Breast Cancer Stem Cells" were searched in Gene Expression Omnibus（GEO）database，and GSE98239 chip data were obtained through analysis and screening. Then GEO2R online analysis tool was used to obtain the differential genes to draw differential gene heat map and volcano map. The differential gene network map of Epimedii Folium intervention for breast cancer stem cells was constructed by Cytoscape 3.8.0，and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis of drug and disease genes were performed. Human breast cancer MDA-MB-231 cells were divided into 20%，40%，60% Epimedii Folium drug-containing serum group and control group. Cell counting kit-8（CCK-8），and Western blot were used to detect the effect of Epimedii Folium drug-containing serum intervention on cell activity and target protein expression in breast cancer cells. Result:Twenty-three active components including flavones，sterols，alkaloids and sesquiterpenoids were obtained from Epimedii Folium. It was found that Epimedii Folium interacted with B-cell lymphoma-2-like protein 1（BCL2L1），matrix metallopeptidase 2（MMP2），prostaglandin-endoperoxide synthase 2（PTGS2），vascular endothelial growth factor A（VEGFA），transforming growth factor beta receptor 1（TGFBR1） and other pivotal genes in breast cancer stem cells，participated in the induction of new angiogenesis and cell migration，enabled the continuous self-renewal of BCSCs，decreased apoptosis and cell migration，thus promoting the recurrence and metastasis of breast cancer. KEGG results showed that Epimedii Folium intervened in multiple differential expressed genes（DEGs）of transforming growth factor-<italic>β</italic>（TGF-<italic>β</italic>），vascular endothelial growth factor（VEGF），phosphoinositide 3kinase/protein kenase B（PI3K/Akt），mitogen-activated protein kinese（MAPK）and mammalian target of rapamycin（mTOR）subpathways in cancer signaling pathways to exert its efficacy in intervening breast cancer stem cells. Experiments showed that the survival rate of breast cancer cells was significantly reduced and the expression levels of TGFBR1 and Smad2 in breast cancer cells significantly decreased after the intervention of Epimedii Folium drug-containing serum（<italic>P</italic><0.01）. Conclusion:Several components in different concentrations of drug-containing serum of Epimedii Folium can synergistically act on target differentially expressed genes of breast cancer stem cells，and inhibit the proliferation of breast cancer cells by down-regulating the expression levels of TGFBR1，a key molecule in the TGF-<italic>β</italic> pathway，and Smad2，a downstream signal.

Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway / 中国中药杂志

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

Discrepancies between total and anterior corneal high-order aberrations at measured and theoretical pupil diameter / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the difference between total and anterior corneal high-order aberrations(HOA)calculated based on the pupil diameters of 4.0mm and the actual measurements in different age groups.<p>METHODS:<i> </i>A cross sectional study. A Total of 100 subjects between March, 31^th and May, 31^th in 2019 were included. Their total corneal high-order aberrations(THOA)and anterior corneal high-order aberrations(AHOA)were detected on the basis of different machine-provided pupil diameters(2.0-7.0mm)and their photopic pupil diameters were recorded as measured pupil diameters in the room with normal illumination. THOA and AHOA based on the machine-measured pupil diameter was calculated through fitting curves, and compared to the THOA and AHOA at a theoretical 4mm pupil diameter.<p>RESULTS: The measured pupil diameter was negatively correlated with age(<i>r</i>= -0.587, <i>P</i><0.001). THOA and AHOA based on measured pupil diameter were both negatively correlated with age(<i>r</i>= -0.191, <i>P=</i>0.002; <i>r</i>=-0.181, <i>P</i>=0.004). At 4mm pupil diameter, THOA was positively correlated with age(<i>r</i>=0.282, <i>P</i><0.001), while there was no obvious correlation between AHOA and age. In 40-49, 60-69 and 70-79 years old groups, their THOA and AHOA at the measured pupil diameters were significantly lower than those at 4mm pupil diameter(<i>P</i><0.05), while their THOA were significantly higher than AHOA at the measured pupil diameters(<i>P</i><0.05). At 4mm pupil diameter, THOA were significantly lower than AHOA in 20-29 years old groups(<i>P</i>=0.006), but higher than AHOA in 60-69 years old groups(<i>P</i>=0.039). In the aged group(include 60-69 and 70-79 years old groups), the proportion of observed value of THOA ≥0.3μm at the measured pupil diameters were significantly lower than those at 4mm pupil diameter(χ²=4.300, <i>P</i>=0.038).<p>CONCLUSION: THOA and AHOA at the measured pupil diameters in the old subjects are significantly lower than those at 4mm pupil diameter, which could be ascribed to their relatively small actual mean pupil sizes. Our study suggested that the THOA rather than AHOA should be used for the selection of multifocal intraocular lens for cataract patients at measured pupil diameter, so that more aged patients will satisfy the inclusion criteria.

Mobile terminal-based survey on the birth characteristics for Chinese newborns / 北京大学学报(医学版)

OBJECTIVE@#To describe the birth characteristics for Chinese newborns, to assess the feasibility of collecting basic data on maternal and child health, and to conduct relevant epidemiological studies by using mobile terminals.@*METHODS@#From June 2016 to January 2017, pregnant women who delivered in hospitals were recruited in 166 hospitals scattered across 23 provinces of China. The data on their maternal and child health including delivery mode, gestational age and birth weight, were collected by self-administered questionnaires embedded in a mobile application. The incidences or means of cesarean section, preterm birth, birth weight, length and head circumference were calculated and compared with recognized national data, including 2005 Growth Standards for Chinese Children Under 7 Years of Age, 2006 World Health Organization Child Growth Standards and 2014 Chinese Neonatal Birth Weight Standards by Gestational Age.@*RESULTS@#A total of 9 986 women were investigated, among whom those aged ≥35 years accounted for 11.7% and those received well education (college and above) accounted for 70.2%. The rate of cesarean section, preterm delivery, low birth weight and macrosomia were 38.1%, 4.5%, 2.2%, and 7.8%, respectively. The means were (3.33±0.44) kg [male (3.36±0.44) kg, female (3.29±0.43) kg] for birth weight, (50.97±2.32) cm [male (51.04±2.32) cm, female (50.89±2.32) cm] for birth length, and (33.99±1.56) cm [male (34.01±1.57) cm, female (33.97±1.55) cm] for head circumference, respectively. As compared with the national data, the cesarean section rate and birth weights by gestational age for term-born neonates were similar to the latest national data in 2014, while the means of birth weight and length were obviously higher than those of the 2005 Growth Standards for Chinese Children Under 7 Years of Age and 2006 World Health Organization Child Growth Standards.@*CONCLUSION@#As compared with the national data 10 years ago, the mean birth weights for male and female newborns were increased by 40 g and 80 g respectively and mean lengths by 0.6 cm and 1.3 cm, but changes for mean head circumferences were negligible, indicating that the physical health condition for Chinese newborns improved significantly over past 10 years and emerging information technology likely provided a new approach for epidemiological research.

Identification of new fusion genes and their clinical significance in endometrial cancer / 中华医学杂志(英文版)

BACKGROUND@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*METHODS@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*RESULTS@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11-123O10.4-GRIP1, RP11-444D3.1-SOX5, RP11-680G10.1-GSE1, NRIP1-AF127936.7, RP11-96H19.1-RP11-446N19.1, and DPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7 and DPH7-PTP4A3 were found only in stage III patients with EC. DPH7-PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*CONCLUSION@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7 and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.

Intra-tumor heterogeneity for endometrial cancer and its clinical significance / 中华医学杂志(英文版)

BACKGROUND@#Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.@*METHODS@#A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.@*RESULTS@#The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. CONCLUSIONS:: Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Clinical effects of anti-VEGF combined with Ahmed valve implantation and phacoemulsification or not for neovascular glaucoma with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To compare the efficacy of anti-VEGF combined with Ahmed valve implantation with phacoemulsification or not for neovascular glaucoma(NVG)with cataract. <p>METHODS: Totally 47 patients(47 eyes)of NVG with cataract were given intraocular injection of anti-VEGF before the surgery, and then treated with Ahmed valve implantation. 19 cases(19 eyes)combined with phacoemulsification, and single Ahmed valve implantation in 28 cases(28 eyes). The vision, IOP, anti-glaucoma medicines and complications of the two groups were recorded and compared with 6mo postoperatively. <p>RESULTS:The IOP of all cases at all time points after surgery was significantly decreased after surgery(<i>P</i> <0.05). 6mo after surgery, in the combined group, the vision was improved in 10 cases(10 eyes)(53%), unchanged in 8 cases(8 eyes)(42%)and decreased in 1 case(1 eye)(5%). The complete success rate was 84%(16/19), the conditional success rate was 11%(2/19), and the failure rate was 5%(1/19). In the single Ahmed valve group, the vision was improved in 11 cases(11 eyes)(39%), unchanged in 17 cases(17 eyes)(61%), decreased in 0 case(0 eye)(0%), complete success rate in operation was 61%(17/28), conditional success rate was 25%(7/28), and the failure rate was 14%(4/28).<p>CONCLUSION: Compare with anti-VEGF with Ahmed vlave implantation, combined with phacoemulsification can effectively control the postoperative IOP, improve the BCVA of the patient as much as possible, reduce the amount of the postoperative glaucoma medicament use, and facilitate the follow-up of the fundus of the patient. It is a efficacy treatment for NVG with cataract.

Intra-tumor heterogeneity for endometrial cancer and its clinical significance / 中华医学杂志(英文版)

Background@#Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.@*Methods@#A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.@*Results@#The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc.@*Conclusions@#Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Identification of new fusion genes and their clinical significance in endometrial cancer / 中华医学杂志(英文版)

Background@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*Methods@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*Results@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11–123O10.4–GRIP1, RP11–444D3.1–SOX5, RP11– 680G10.1–GSE1, NRIP1–AF127936.7, RP11–96H19.1–RP11–446N19.1, and DPH7–PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1–AF127936.7 and DPH7–PTP4A3 were found only in stage III patients with EC. DPH7–PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*Conclusion@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1– AF127936.7 and DPH7–PTP4A3 might be related to stage, and DPH7–PTP4A3 be related to grade and recurrence.

Effect of miR-145 over-expression on radiosensitivity of cervical cancer cells / 中国病理生理杂志

AIM:To investigate the molecular mechanism of microRNA(miR)-145 enhancing radiosensitivity of cervical cancer cells.METHODS:Cervical cancer lines HeLa,CaSki,C33A and SiHa were transfected with miR-145-mimic and NC-mimic using Lipofectamine 2000 kit,and the expression levels of miR-145 in the cervical cancer lines and endometrial stromal cells(ESC)were detected by real-time PCR.The transfected cells were exposed to X-ray radiation.At different time points,the cell viability and apoptotic rate were measured by MTT assay and flow cytometry with AnnexinV -FITC/PI staining,respectively.The protein levels of γH2AX and helicase-like transcription factor(HLTF)were monitored by immunofluorescence and Western blot, respectively.RESULTS: High miR-145 levels was found in ESC, while low miR-145 levels were found in HeLa,SiHa,C33A and CaSki cells.The level of miR-145 in the cells transfected with miR-145-mimic was significantly higher than that in the negative control cells(P<0.05).The viability of cervical cancer cells with miR-145 over-expression was notably lower than that of the negative control cells, and the apoptotic rate at 72 h was remarkablely increased(P<0.05)under the same condition.The results of immunofluorescence labeling indicated that the protein level of γH2AX significantly increased in the cervical cancer cells with miR-145 over-expression exposed to radia-tion compared with the negative control cells(P<0.05).The results of Western blot indicated that the protein level of HLTF significantly decreased in the cervical cancer cells with miR-145 over-expression compared with the negative control cells(P<0.05).CONCLUSION:miR-145 was highly expressed in normal endometrial epithelial cells, while low ex-pressed in cervical cancer cells.miR-145 over-expression inhibits growth and significantly enhances radiosensitivity of cer -vical cancer cells.The molecular mechanism is possiblely related to downregulating HLTF expression and inhibiting DNA damage repair,thus resulting in apoptosis.

Dual-specificity Phosphatase 1 Deficiency Induces Endometrioid Adenocarcinoma Progression via Activation of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previously, we reported that dual-specificity phosphatase 1 (DUSP1) was differentially expressed in endometrioid adenocarcinoma (EEA). However, the role of DUSP1 in EEA progression and the relationship between DUSP1 and medroxyprogesterone (MPA) are still unclear.</p><p><b>METHODS</b>The expression of DUSP1 in EEA specimens was detected by immunohistochemical analysis. The effect of DUSP1 on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSP1 expression in EEA cells was measured by Western blot.</p><p><b>RESULTS</b>DUSP1 expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines (Hec1A, Hec1B, RL952, and Ishikawa), the DUSP1 expression was substantially higher in Ishikawa cells than in other cell lines (P < 0.05). Knockdown of DUSP1 promoted Ishikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/Erk) pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells.</p><p><b>CONCLUSIONS</b>Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP1 may serve as a potential therapeutic target for the treatment of EEA.</p>

The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75-80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence.</p><p><b>METHODS</b>We performed a retrospective review of 296 patients diagnosed with Stage IA-IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy.</p><p><b>RESULTS</b>The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM.</p><p><b>CONCLUSIONS</b>Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI, parametrial invasion, and depth of cervical stromal invasion were identified as independent clinicopathological risk factors for pelvic LNM.</p>

Study on transport mechanism of baicalin in Scutellariae radix extracts and effect of Angelica dahurica extracts on transport of baicalin by Caco-2 cell monolayer model / 中国中药杂志

<p><b>OBJECTIVE</b>To study the transport mechanism of baicalin of Scutellariae Radix extracts and the effect of Angelica dahurica extracts on the intestinal absorption of baicalin by using Caco-2 cell monolayer model, in order to analyze the effect mechanism of Angelica dahurica extracts on the intestinal absorption of baicalin.</p><p><b>METHOD</b>The Caco-2 cell monolayer model was established with human colonic adenocarcinoma cells, and used to study the effect of pH, time, drug concentration and temperature on the transport of baicalin in Scutellariae Radix extracts, the effect of P-gp and MRP protein-dedicated inhibitors on the bidirectional transport of baicalin in Caco-2 cell model, and the effect of angelica root extracts on baicalin absorption and transport.</p><p><b>RESULT</b>Baicalin was absorbed well at 37 degrees C and under pH 7.4 condition and concentration dependent. Its proteins became inactive at 4 degrees C, with a low transport. The bi-drectional transfer PDR was 0. 54. After P-gp inhibitor verapamil and MRP inhibitor probenecid were added, the value of PappBL-AP of baicalin decreased, but without any difference in PDR. The transport of baicalin was improved by 2.34, 3.31 and 3.13 times, after A. dahurica extract coumarin, volatile oil, and mixture of coumarin and volatile oil.</p><p><b>CONCLUSION</b>The transport mechanism of baicalin is mainly passive transfer and supplemented with efflux proteins involved. A. dahurica extracts can enhance the absorption of baicalin, which may be related to the passive transfer merchanism of baicalin. A. dahurica extracts' effect in opening the close junction among cells may be related to its expression or function in inhibiting efflux proteins.</p>

Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma.</p><p><b>METHODS</b>Ninety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People's Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics (FIGO) stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays (SAM) was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by χ(2) test.</p><p><b>RESULTS</b>Analysis between FIGO 1988 stage I and stage III identified a 362-gene "progress signature"; 171 down-regulated and 191 up-regulated genes. Among the alterative genes, TARP (T cell receptor gamma alternate reading frame protein) and KRT5 (keratin 5) decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased (P < 0.05). The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased (P < 0.05). In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ (both P < 0.05) both. The expression of P53 had a negative relationship with the expression of KRT5 (P < 0.05), but not with the expression of TARP (P > 0.05). There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN (all P > 0.05). There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 (P > 0.05).</p><p><b>CONCLUSION</b>The expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.</p>

Effects of insulin, insulin-like growth factor-I and -II on proliferation and intracellular signaling in endometrial carcinoma cells with different expression levels of insulin receptor isoform A / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperinsulinemia, insulin-like growth factor (IGF)-I and -II (IGF-II) are associated with increased risk of endometrial carcinoma. Insulin receptor isoform A (IR-A) is more frequently expressed in endometrial carcinoma than in normal endometrial tissues. To better understand their roles in endometrial carcinoma, we investigated the effects of insulin, IGF-I, and IGF-II in endometrial carcinomas cells with different IR-A expression levels.</p><p><b>METHODS</b>To explore the role of IR-A in mediating the activity of IGF-I, IGF-II, and insulin, we investigate the cellular proliferation of endometrial carcinoma cell lines RL95-2 and RL95-2-IR-A by MTS assays. Then we examined the protein kinase Akt phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in both cell lines by Western blotting. The effect of IGF-II and AG1024 on cell cycle progression and apoptosis was assessed by flowcytometry. To examine whether the effects of IGFs were mediated by IR-A, we blocked IGF-I receptor (IGF-IR) in both cell lines using AG1024, an IGF-IR-specific inhibitor.</p><p><b>RESULTS</b>IGF-I and IGF-II significantly enhanced proliferation of both cell lines (P < 0.05). By contrast, insulin significantly increased proliferation of RL95-2-IR-A cells only (P < 0.05). IGF-I and IGF-II significantly increased pAkt levels in RL95-2 cells and pERK1/2 levels in RL95-2-IR-A cells (all, P < 0.05). Insulin increased pERK1/2 levels in RL95-2-IR-A cells only (P < 0.05). LY294002 and PD98059 inhibited the specific signaling activities and cellular proliferation. After AG1024 pretreatment, neither IGF-I nor IGF-II affected pAkt levels in RL95-2 cells. IGF-II, but not IGF-I, increased pERK1/2 levels in RL95-2-IR-A cells. After AG1024 pretreatment, the proliferation rate and DNA content corresponding to the S phase increased and apoptosis decreased significantly in IGF-II-treated RL95-2-IR-A cells only (P < 0.05).</p><p><b>CONCLUSIONS</b>The proliferation effect of insulin is mediated by IR-A. When IR-A dominates in a cell line, IGF-II activated cell proliferation mainly through the ERK1/2 pathway. On the other hand, IGF-II activated cell proliferation mainly through the Akt pathway. IR-A can at least partly mediate the proliferative and anti-apoptotic effects of IGF-II through the ERK1/2 pathway.</p>

National annual monitoring report of drinking-water-borne endemic fluorosis in 2010 and 2011 / 中国地方病学杂志

Objective To grasp the operation quality of the water-improving projects for lowing fluoride level and to grasp the prevalence trend of fluorosis in drinking-water-borne fluorosis affected areas in China.Methods According to theSurveillance Scheme of Drinking-Water-Borne Endemic Fluorosis(Trial),314 counties were selected as monitoring counties in 2010 and 2011,respectively.Ten water-improving projects were randomly selected in each monitoring county every year.For each project,the operating condition was investigated and the fluoride level of tap water was determined.For each village,the fluoride level in drinking water was determined and the prevalence of dental fluorosis of all pupils aged 8-12 were surveyed.Dental fluorosis was diagnosed according to Dean method.Results ①A total of 1381 water-improving projects were monitored in 2010,among which normal operating projects accounted for 93.19％ (1287/1381) and those with qualified fluoride level accounted for 76.32％ (1054/1398).A total of 1408 water-improving projects were monitored in 2011.Normal operating projects accounted for 94.74％(1334/1408) and those with qualified fluoride level accounted for 79.26％ (1116/1408).②Total 319 villages with water-improving projects were monitored in 2010,and the number in 2011 was 327.The qualification rate of water fluoride content for 2010 and 2011 were 73.35％ (234/319) and 73.70％ (241/327),respectively.Total 84 villages without water-improving projects were monitored in 2010,and the number in 2011 was 88.Villages with fluoride level ＞ 1.2-2.0 mg/L,＞ 2.0-4.0 mg/L,and ＞ 4.0 mg/L in 2010 accounted for 47.62％ (40/84),42.86％ (36/84),and 9.52％ (8/84),respectively.The proportion in 2011 was 52.27％(46/88),38.64％(34/88),and 9.09％(8/88),respectively.③The detectable rates of dental fluorosis of children aged 8-12 in 2010 and 2011 were 26.97％(4347/16 119) and 24.98％(4027/16 123),respectively.In the monitored villages,the water-improving projects were under normal operation and fluoride content in water was qualified.And the rates for villages with water-improving projects under abnormal operation or fluoride content in water unqualified in 2010 and 2011 were 44.09％ (1721/3903) and 41.86％ (2188/5227),respectively.While the rates for villages without water-improving projects in 2010 and 2011 were 46.08％ (2802/6081) and 45.51％ (2804/6161),respectively.Conclusions The national normal operation rates of water-improving projects for lowing fluoride level are between 93％ and 95％.The qualification rate of fluoride content in drinking water is lower than 80％.The operation condition and water quality of the water-improving projects in China need to be improved.The prevalence of children dental fluorosis of affected villages has dropped significantly after low fluoride water is provided continuously.

Annual monitoring report of national drinking-water-borne endemic arsenicosis in 2010 and 2011 / 中国地方病学杂志

Objective To provide a basis for preventive strategies to national drinking-water-borne endemic arsenicosis through mastering the implementing progress of preventive measures and observing the dynamic changes.Methods Surveillances were carried out according to the provisions and requirements of The Surveillance Project for National Drinking-Water-Borne Endemic Arsenicosis(Trial).Total of 11 provinces(autonomous regions) and Xinjiang Production and Construction Corps were selected as the surveillance provinces (autonomous regions).Endemic arsenicosis villages with exposed population over 100 persons were chosen as monitoring villages in each province,81 villages in 2010 and 89 villages in 2011 were selected.Potential endemic arsenicosis villages with exposed population over 100 persons were included; 26 villages in 2010 and 19 villages in 2011 were selected.The operation of water-improving projects was investigated,the arsenic content in water from resident house was tested in potential endemic arsenicosis villages and the prevalence of endemic arsenicosis based on the residents who lived in monitoring villages was surveyed:Results ①Total of 225 water-improving projects in 45 counties were monitored,1349 villages were covered and 72.66 million persons were benefited in 2010.Total of 233 waterimproving projects in 48 counties were monitored,1576 villages were covered and 84.61 million persons were benefited in 2011.②)Total of 107 villages with high level of water arsenic were investigated and 81 villages had improved the water quality in these villages in 2010.The water-improving projects running normally reached 90.12％(73/81),intermittent operation rate was 9.88％ (8/81) and without abandoned projects.The projects with qualified water reached 86.42％ (70/81).Total of 108 villages with high level of water arsenic were investigated and 89 villages with water improved in 2011.Normally operated projects reached 86.52％ (77/89),intermittent operation rate was 11.24％ (10/89)and abandoned projects was 2.25％ (2/89).The projects with qualified water arsenic level reached 82.02％(73/89).In addition,26 villages without water-improvement were investigated in 2010,and the families with high level of water arsenic reached 66.01％(371/562).Total of 19 villages were surveyed in 2011,and the families with high level of arsenic reached 54.99％(204/371).③Total of 23 964 persons were examined in villages with improved water in 2010,the detection rate of patients with endemic arsenicosis was 4.43％ (1061/23 964),3964 persons were examined in the villages without water-improvement and the detection rate was 5.98％(237/3964),two new cases were diagnosed.Total of 25 225 persons were examined in villages with waterimproved,the detection rate was 4.68％(1181/25 225),3145 persons were examined in the villages without waterimprovement,and the detection rate was 2.26％(71/3145) in 2011,none new case was detected.Conclusions It is not optimistic about the operating status and quality of water-improving projects.The prevalence in water-improved villages remains higher than that in water-unimproved villages.The long-term mechanism of surveillance should be established and perfected as soon as possible,and the management and maintenance of water-improving projects also should be strengthened.

Bronchoscopy in some tertiary grade A hospitals in China: two years' development / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although bronchoscopy has been widely performed in China, little has been known about its current state and development. In order to investigate the clinical application of bronchoscopy and make instructions for future education and development, the Chinese Society of Respiratory Diseases conducted postal surveys in both 2008 and 2010 in China.</p><p><b>METHOD</b>Questionnaires were sent to 40 tertiary grade A hospitals in 2008 and 58 tertiary grade A hospitals in 2010 to investigate bronchoscopies performed in 2007 and 2009 respectively.</p><p><b>RESULTS</b>Thirty (75%) hospitals returned the completed questionnaires in 2008 and forty-one (71%) hospitals in 2010. All the respondents possessed flexible bronchoscopes. Fifty percent of the respondents had less than five in 2007, while more than 50% of the respondents had 5-9 bronchoscopes in 2009. All the respondents performed a radiograph or CT scan before bronchoscopy. Percentage of general anesthesia and no pre-medication before bronchoscopy increased, while atropine usage decreased in 2009 compared to 2007. During bronchoscopy, pulse oximetry was the most widely used monitoring method. Most respondents used the nasal route to perform routine bronchoscopy. After the procedure, they used sinks to wash and glutaraldehyde to disinfect the bronchoscopes. The total number of flexible bronchoscopies performed during 2007 was 37 874 and the average was 1262. Whereas in 2009, the total number was 60 178 and the average was 1468. Diagnostic bronchoscopy was more widely used than therapeutic bronchoscopy. The mortality rate was 0.076‰ in 2007 and 0.032‰ in 2009.</p><p><b>CONCLUSIONS</b>The two surveys, to some extent, reflected the current status and development of bronchoscopy in China. The results are worthy of future education and developing of new guidelines. Regular surveys and monitoring of bronchoscopies across China are needed.</p>

Histone deacetylase inhibitors inducing human cervical cancer cell apoptosis by decreasing DNA-methyltransferase 3B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Histone deacetylase (HDAC) inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, apoptosis, cell differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis. However, the mechanisms of apoptosis effect are not fully understood. TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this study, we selected Trichostatin A (TSA) to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells.</p><p><b>METHODS</b>Cervical cancer cell lines such as Hela, Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal violent assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine cell number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase (DNMT)1, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western Blotting. Small interfering RNA (SiRNAi) was used to knock down DNMT3B.</p><p><b>RESULTS</b>HDAC inhibitors only induce cervical cancer cell apoptosis. At 1 µmol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, (90.0 ± 8.4)% of normal cell survive after treated with 1 µmol/L of TSA. We compared 1 µmol/L group with untreated control with t-test. There was no significance between 1 µmol/L group and untreated control for normal cell (P > 0.05). HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B.</p><p><b>CONCLUSIONS</b>DNMT3B was essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC inhibitors may play an important role in the toxicity of HDAC inhibitors on cervical cancer cells.</p>