0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period.

BACKGROUND: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. METHODS: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. RESULTS: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. CONCLUSIONS: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. CLINICAL TRIAL NUMBER AND REGISTRY URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022.

Median nerve block increases the success rate of radial artery cannulation in women with gestational hypertension undergoing cesarean section.

BACKGROUND: The radial artery cannulation helps to maintain the stability of maternal hemodynamics and reduce complications, however, it is difficult for women with gestational hypertension. Ultrasound-guided median nerve block can cause arterial vasodilation, which may improve the success rate of radial artery cannulation. METHODS: Ninety-two women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed ultrasound-guided cannulation were identified and randomized into the median nerve block group and control group. Median nerve block was performed under the guidance of ultrasound in the middle forearm and 5 ml of 0.5% lidocaine was injected. Subcutaneous local block was administered in the control group. The ultrasound-guided radial artery cannulation was performed ten minutes after blocking. Baseline measurements (T1) were performed after 10 minutes of rest. All variables were measured again at 10 (T2) and 30 (T3) minutes after median nerve block or local block. The primary outcome was the success rate of radial artery cannulation within 10 minutes after blocking. The puncture time, number of attempts, the overall complications, and ultrasonographic measurements including radial artery diameter and cross-sectional area were recorded before (T1), 10 minutes (T2) after, and 30 minutes (T3) after block. RESULTS: A total of 92 pregnant women were identified and completed the follow-up. As compared to control group, the first-attempt success rate of radial artery cannulation was significantly higher (95.7% vs78.3%, p = 0.027) and procedure time to success was significantly shorter (118 ± 19 s vs 172 ± 66 s, p < 0.001) in median nerve group. Median nerve group also had a significantly less overall number of attempts (p = 0.024). Compared with control group, the diameter and cross-sectional area of radial artery increased significantly at the T2 and T3 points in median nerve group (p < 0.001), as well as percentage change of radial artery diameter and CSA. No difference was observed in the overall complication at chosen radial artery, which including vasospasm (21.7% vs 28.3%; p = 0.470) and hematoma (4.3% vs 8.7%; p = 0.677). CONCLUSIONS: Ultrasound-guided median nerve block can increase the first-attempt success rate of chosen radial artery cannulation in women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed radial artery cannulation, and especially for those anesthesiologists with less experienced in radial artery cannulation. TRIAL REGISTRATION: ChiCTR2100052862; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 06/11/2021.

Comprehensive expression-based isoform biomarkers predictive of drug responses based on isoform co-expression networks and clinical data.

Drug sensitivity biomarkers are molecular features informative for drug response. Previous studies have identified many candidate drug-sensitivity signatures at the transcript level based on significant p values. However, the potential of sensitivity biomarkers has not been sufficiently understood because these investigations have focused on individual biomarkers and have not been carried out at the systems level. In this study, we applied a meta-analytical framework to compute co-expression between isoform pairs in two large datasets of RNA-seq profiles of breast cancer cell lines. We then built hallmark-related direct (HRD) networks by integrating a breast cancer specific isoform co-expression (BCIC) network and hallmark-related isoforms. Next, we explored the associations between isoform biomarkers and the functional clusters of the HRD network. The crucial isoform-based biomarkers for drugs were identified by functional clusters analysis and elucidated by combining isoform expression profiles with clinical information for breast cancer in The Cancer Genome Atlas.

Unraveling the signaling network between dysregulated microRNA and mRNA expression in sevoflurane-induced developmental neurotoxicity in rat.

Research has indicated that general anesthesia may cause neuroapoptosis and long-term cognitive dysfunction in developing animals, however, the precise mechanisms orchestrating these outcomes remain inadequately elucidated within scholarly discourse. The purpose of this study was to investigate the impact of sevoflurane on the hippocampus of developing rats by analyzing the changes in microRNA and mRNA and their interactions. Rats were exposed to sevoflurane for 4 h on their seventh day after birth, and the hippocampus was collected for analysis of neuroapoptosis by Western blot and immunohistochemistry. High-throughput sequencing was conducted to analyze the variances in miRNA and mRNA expression levels, and the Morris water maze was employed to assess long-term memory in rats exposed to sevoflurane after 8 weeks. The results showed that sevoflurane exposure led to dysregulation of 5 miRNAs and 306 mRNAs in the hippocampus. Bioinformatic analysis revealed that these dysregulated miRNA-mRNA target pairs were associated with pathological neurodevelopment and developmental disorders, such as regulation of axonogenesis, regulation of neuron projection development, regulation of neuron differentiation, transmission of nerve impulse, and neuronal cell body. Further analysis showed that these miRNAs formed potential network interactions with 44 mRNAs, and two important nodes were identified, miR-130b-5p and miR-449c-5p. Overall, this study suggests that the dysregulation of the miRNA-mRNA signaling network induced by sevoflurane may contribute to neurodevelopmental toxicity in the hippocampus of rats and be associated with long-term cognitive dysfunction.

Subcutaneous nitroglycerin increased the success rate of radial artery cannulation in women with gestational hypertension undergoing cesarean section : A randomized controlled trial.

BACKGROUND: Radial artery cannulation helps to maintain the stability of maternal hemodynamics and reduce complications; however, it is difficult for women with gestational hypertension. Subcutaneous nitroglycerin was found to improve the first attempt success rate of radial artery cannulation in pediatric patients. Therefore, this study evaluated the effect of subcutaneous nitroglycerin on the radial artery diameter and area, blood flow rate and the success rate of radial artery cannulation in women with pregnancy-induced hypertension. METHODS: A total of 94 women with gestational hypertension and risk of intraoperative bleeding undergoing cesarean section were identified and randomized into the subcutaneous nitroglycerin group and control group. The primary outcome was the success rate of left radial artery cannulation within 3 min after subcutaneous injecting (T2). The puncture time, number of attempts, the overall complications, and ultrasonographic measurements including radial artery diameter, cross-sectional area and depth were also recorded before subcutaneous injection (T1), 3 min after subcutaneous injection (T2) and immediately after radial artery cannulation (T3). RESULTS: The first attempt success rate of radial artery cannulation was significantly higher (97.9% vs. 76.6%, p = 0.004) and procedure time to success was significantly shorter (111 ± 18 s vs. 171 ± 70 s, p < 0.001) in the subcutaneous nitroglycerin group as compared to the control group. The subcutaneous nitroglycerin group also had a significantly less overall number of attempts as 1/2/3 attempts (n), 46/1/0 vs. 36/7/4 (p = 0.008). Compared with the control group, the diameter and cross-sectional area of radial artery increased significantly at the T2 and T3 points in the subcutaneous nitroglycerin group (p < 0.001), as well as percentage change of radial artery diameter and CSA. Vasospasm (6.4% vs. 31.9%; p = 0.003) was significantly lower in the subcutaneous nitroglycerin group; however, no difference was found in hematoma (2.1% vs. 12.8%; p = 0.111). CONCLUSION: Subcutaneous nitroglycerin along with the routine local anesthetic preparation before radial artery cannulation increased the first attempt success rate of radial artery cannulation and decreased the overall number of cannulation attempts in women with gestational hypertension and risks of intraoperative bleeding undergoing cesarean section, it also decreased cannulation times and overall number of vasospasms.

Changes in palaeoclimate and palaeoenvironment in the Upper Yangtze area (South China) during the Ordovician-Silurian transition.

The Ordovician-Silurian transition was a critical period in geological history, during which profound changes in climatic, biotic, and oceanic conditions occurred. To explore the provenance, palaeoclimate, and palaeoredox conditions in the Sichuan Basin during the Late Ordovician-early Silurian interval, we conducted mineralogical, geochemical, and isotopic analyses of three formations (Wufeng, Guanyinqiao and Longmaxi formations) in the Xindi No. 2 well. The ternary and bivariate diagrams indicate that the provenance is mainly felsic igneous rocks and originated mainly from a collisional setting, presumably due to an active continental margin. The chemical index of alteration (CIA) values in the lower Wufeng and Longmaxi formations are relatively high (67.48-73.57), indicating a warm and humid climate. In contrast, the CIA values declined rapidly (58.30-64.66) during the late Katian to early Hirnantian, which had a fluctuating cold and dry climate and was interrupted by a transient warm and humid climate. The palaeoredox indices (Mo concentrations and Moauth/Uauth, U/Th, V/Cr, Ni/Co, and V/V + Ni values) during the Late Ordovician-early Silurian indicate two cycles of water column euxinia. The first cycle occurred during Wufeng Formation deposition, with bottom waters evolving from oxic-suboxic to suboxic-anoxic. Most samples show relatively low redox-sensitive trace element concentrations during the Guanyinqiao Formation, pointing to oxic-suboxic conditions. The second cycle, during the late Hirnantian, transitioned from oxic to euxinic water conditions. Our δ13Corg data are comparable to previously reported records and exhibit a strong correlation between the Hirnantian isotopic carbon excursion (HICE), climate change, and redox conditions. We suggest that the variations in the δ13C values are related to two elements: (1) increased photosynthetic activity under oxic water conditions, and (2) increased carbonate weathering exposed by the glacio-eustatic sea- level. In addition, the high δ13Corg values might indicate a more shelf-proximal setting during Xindi No. 2 well deposition. The δ13Corg isotopic data effectively constrain the timing of the Late Ordovician mass extinction (LOME) and the evolution of the temporal changes in the climatic and ocean redox conditions, suggesting an apparent stratigraphic coincidence between climate and redox fluctuations and two-phase extinctions, which implies a strong causal relationship. The LOME was systematically driven by the combination of cooler glacial temperatures, glacio-eustatic sea-level fluctuations, and anoxic water conditions that caused the two pulses of extinction in the Yangtze shelf sea.

Application Analysis of Multiacupoint Stimulation in Multimodal Labor Analgesia during the Whole Stage of Labor in Primipara.

Purpose: To analyze the application value of multimodal analgesia (MMA) regimen of patient-controlled epidural analgesia (PCEA) combined with multiacupoint stimulation analgesia during the whole stage of labor analgesia in primipara. Methods: 300 primiparas with natural delivery were selected. According to the different ways of labor analgesia, they were divided into the first stage of labor active period PCEA group (group A), the whole stage of labor PCEA group (group W), and the whole stage of labor PCEA combined with multiacupoint stimulation analgesia group (group WM). The effect of MMA during the whole-labor process on maternal and infant safety was evaluated. The specific observation indicators were as follows: visual analogue scale (VAS) scores before analgesia (T 0), at full opening of the uterus (T 1), at the end of the second stage of labor (T 2), and at the end of the third stage of labor (T 3); stress response indicators at T 0 and T 1: epinephrine (E), norepinephrine (NE), glucose (Glu), and ß-endorphin (ß-EP) levels; delivery time of each stage of labor; the Apgar score of newborns at 1 and 5 min after birth; indicators of umbilical artery blood gas analysis immediately after delivery: PH value, base excess (BE), partial pressure of oxygen (PaO2), and partial pressure of carbon dioxide (PaCO2); incidence of postpartum depression (PPD) at 6 weeks after delivery. Results: At T 1, T 2, and T 3, the VAS scores were lower in groups W and WM than in group A, and the VAS scores were lower in group WM than in group W (P < 0.05). At T 0, there was no significant difference in the comparison of E, NE, Glu, and ß-EP levels among the three groups (P > 0.05). At T 1, the levels of E, NE, Glu, and ß-EP were higher in the three groups than in the same group at T 0, the levels of E, NE, and Glu were lower, the levels of ß-EP were higher in groups W and WM than in group A, and the levels of ß-EP were higher in group WM than in group W (P < 0.05). Comparing the delivery time of the first stage of labor in the three groups, groups A and WM were shorter than group W (P < 0.05). Comparing the delivery time of the second and third stages of labor in the three groups, there was no significant difference (P > 0.05). Comparing the Apgar scores of the three groups of newborns at 1 and 5 min after birth, there was no significant difference (P > 0.05). Comparing the incidence of newborn asphyxia in the three groups, there was also no significant difference (P > 0.05). Comparing the PH, BE, PaO2, and PaCO2 of three groups of newborns after delivery, there were no significant differences (P > 0.05). At 6 weeks after delivery, the incidence of PPD was lower in groups W (10.00%) and WM (8.00%) than in group A (20.00%) (P < 0.05). Conclusion: The application of the MMA regimen of PCEA combined with multiacupoint stimulation for labor analgesia during the whole stage of labor in primipara can effectively reduce labor pain and stress response during the whole stage of labor and shorten the delivery time of the first stage of labor, the indicators of newborn Apgar score and umbilical artery blood gas analysis are not affected, and the incidence of PPD in patients is reduced, which can play a protective role for the safety of mother and infant.

The Changes of Brain Function After Spinal Manipulation Therapy in Patients with Chronic Low Back Pain: A Rest BOLD fMRI Study.

OBJECTIVE: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated. RESULTS: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = -0.549, -0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01). CONCLUSION: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.

Overexpression of TMEM47 Induces Tamoxifen Resistance in Human Breast Cancer Cells.

BACKGROUND: Tamoxifen (TAM) is the eminent first-line drug for endocrine therapy of hormone receptor positive premenopausal breast cancer and reduces the risk of recurrence by ∼50%. However, many patients developed TAM resistance and their diseases recurred. Our previous study on transcriptome profile of TAM resistant breast cancer cells revealed that the TMEM47 is one of the most significantly differentially expressed genes. The mechanism of how TMEM47 is involved in TAM resistance was not known. METHODS: We constructed a mammal breast cancer cell line, in which TMEM47 was stably overexpressed (TMEM47-OE/MCF-7), to further verify the role of TMEM47 in TAM resistance. siRNA targeting TMEM47 was transfected into TAMR / MCF-7 cells by Liposome. TMEM47 expression was validated on mRNA and protein level by qRT-PCR and western blotting. We tested the cytotoxicity of TAM in the cells. Apoptosis was detected by flow cytometry. RESULTS: Compared to the MCF7 cells, TMEM47 mRNA was significantly up regulated more than 6 folds in the TAMR/MCF7 cells and so its protein. TMEM47 expression level in TMEM47-OE/MCF-7 was similar as in the TAMR/MCF-7 cells. The 50% inhibitory concentration (IC50) value (mean ± SD) of TAM in MCF-7, TAMR/MCF-7 and TMEM47-OE/MCF-7 cells was 1.58 ± 0.19, 2.74 ± 0.24 and 3.12 ± 0.32 µÎ³/mL, respectively. The apoptosis rates of TAMR/MCF-7 and TMEM47-OE/MCF-7 cell lines were significantly lower than that of MCF-7 cells. After 24 and 48 hours TAM treatments, cell viability was significantly inhibitied in TMEM47 knockdown TAMR/MCF7 cells (P < 0.01). Consistant with the decreased cell viability, the apoptosis rate in TMEM47 knockdown TAMR/MCF-7 cells was significantly increased. CONCLUSIONS: Our results suggest that overexpression of TMEM47 in MCF-7 cells acquired TAM resistance to those cells, and knockdown of TMEM47 in TAMR/MCF-7 cells reversed their resistance to TAM. TMEM47 might confer TAM resistance on MCF-7 cells through the inhibition of apoptosis.

[Temporal and spatial variations of soil moisture in North China]. / 华北地区土壤水分的时空变化特征.

Soil moisture is an important hydrological parameter and a basic element for research in water cycle and climate change. Using hourly recorded soil moisture data of 374 stations from the new generation of automatic soil moisture encryption observation network constructed by China Meteo-rological Administration, we analyzed the spatial and temporal variations of soil moisture in North China from 2013 to 2019 and the relationship with precipitation and temperature. The results showed that soil moisture in 10-100 cm layer decreased fluctuatly as a whole, with the decreasing at the 100 cm being serious. The spatial distribution of soil moisture at different depths was characterized by high in the southeast and low in the northwest. About 63% of the surface layer was short of moisture. Soil moisture at different depths changed significantly with the seasons. In summer, soil moisture of each layer reached the highest and soil entropy of each layer was suitable, while it reached a low point in spring. Soil moisture was closely correlated with precipitation and temperature, but the correlation got weaker gradually with the increase of soil depth. Soil moisture was more sensitive to precipitation than to temperature.

Pathogen identification in culture-negative cerebrospinal fluid specimens of patients with purulent meningitis using next-generation sequencing technology.

Antimicrobial therapy necessitates fast and accurate detection of pathogens in purulent meningitis (PM) diagnosis. Although considered a gold standard, the traditional bacterial detection and identification methods based on routine bacterial culture are time-consuming and show low sensitivity and specificity. In order to reduce PM-related deaths and improve the treatment efficiency, we employed trace DNA extraction technology and combined it with Next-Generation Sequencing technology for bacteria identification. We extracted DNA from 31 cerebrospinal fluid (CSF) samples from people with PM. The samples were collected by lumbar puncture at Xi'an Children Hospital under a stringent protocol. Ion PGMTM System Next-Generation Sequencing was used to screen for pathogens in the CSF samples based on their 16S ribosomal RNA (rRNA) genes. Of the 31 CSF samples, 29 were culture negative. Streptococcus was detected in 2 samples by culture-based methods. The species identified by Next-Generation Sequencing showed a diverse bacterial population that included Streptococcus (22.6%), Escherichia (15.9%), Peptostreptococcus (10.7%), Pseudomonas (10.5%), Rothia (8.8%), Acinetobacter (4.9%), Prevotella (4.1%), Bacillus (3.3%), Neisseria (2.5%), Catonella (2.4%), Acitinomyces (2.0%), and Citrobacter (2.0%). Clustering analysis revealed three major bacterial groups, namely Streptococcus, Escherichia and Acinetobacter, each group with a different proportion of bacterial species. The results indicated that PM may result from infections by multiple bacterial species as opposed to a single species, with infectivity determined by abundance of the dominant species. Furthermore, Next-Generation Sequencing allowed a sensitive and specific etiological basis for identification of pathogens not only in the cerebrospinal fluid specimens, but also in other clinical samples.

Network-based method for drug target discovery at the isoform level.

Identification of primary targets associated with phenotypes can facilitate exploration of the underlying molecular mechanisms of compounds and optimization of the structures of promising drugs. However, the literature reports limited effort to identify the target major isoform of a single known target gene. The majority of genes generate multiple transcripts that are translated into proteins that may carry out distinct and even opposing biological functions through alternative splicing. In addition, isoform expression is dynamic and varies depending on the developmental stage and cell type. To identify target major isoforms, we integrated a breast cancer type-specific isoform coexpression network with gene perturbation signatures in the MCF7 cell line in the Connectivity Map database using the 'shortest path' drug target prioritization method. We used a leukemia cancer network and differential expression data for drugs in the HL-60 cell line to test the robustness of the detection algorithm for target major isoforms. We further analyzed the properties of target major isoforms for each multi-isoform gene using pharmacogenomic datasets, proteomic data and the principal isoforms defined by the APPRIS and STRING datasets. Then, we tested our predictions for the most promising target major protein isoforms of DNMT1, MGEA5 and P4HB4 based on expression data and topological features in the coexpression network. Interestingly, these isoforms are not annotated as principal isoforms in APPRIS. Lastly, we tested the affinity of the target major isoform of MGEA5 for streptozocin through in silico docking. Our findings will pave the way for more effective and targeted therapies via studies of drug targets at the isoform level.

A Comparative Study of Cluster Detection Algorithms in Protein-Protein Interaction for Drug Target Discovery and Drug Repurposing.

The interactions between drugs and their target proteins induce altered expression of genes involved in complex intracellular networks. The properties of these functional network modules are critical for the identification of drug targets, for drug repurposing, and for understanding the underlying mode of action of the drug. The topological modules generated by a computational approach are defined as functional clusters. However, the functions inferred for these topological modules extracted from a large-scale molecular interaction network, such as a protein-protein interaction (PPI) network, could differ depending on different cluster detection algorithms. Moreover, the dynamic gene expression profiles among tissues or cell types causes differential functional interaction patterns between the molecular components. Thus, the connections in the PPI network should be modified by the transcriptomic landscape of specific cell lines before producing topological clusters. Here, we systematically investigated the clusters of a cell-based PPI network by using four cluster detection algorithms. We subsequently compared the performance of these algorithms for target gene prediction, which integrates gene perturbation data with the cell-based PPI network using two drug target prioritization methods, shortest path and diffusion correlation. In addition, we validated the proportion of perturbed genes in clusters by finding candidate anti-breast cancer drugs and confirming our predictions using literature evidence and cases in the ClinicalTrials.gov. Our results indicate that the Walktrap (CW) clustering algorithm achieved the best performance overall in our comparative study.

Network-based approach to identify principal isoforms among four cancer types.

Protein isoforms are structurally similar proteins produced by alternative splicing of a single gene or genes from the same family. Isoforms of a protein can perform the same, similar, or even opposite biological functions. A previous study identified principal isoforms of proteins based on the extent of interactions per isoform in a functional relationship network, focusing on data from normal tissues. Additionally, the expression levels of specific isoforms of various genes associated with tumorigenesis and prognosis are frequently altered in tumors compared with those in normal tissues. In this study, we aimed to identify higher degree isoforms (HDIs) of multi-isoform genes (MIGs) in cancer by applying a meta-analytical framework to calculate co-expression between each pair of isoforms in two large datasets of RNA-seq profiles from breast cancer, lung cancer, leukemia, and colon cancer cell lines. Then, we compared HDIs with isoforms identified by proteomic data and prognostic and predictive evidence in various cancers. In addition, we separately analyzed the associations between HDIs and non-HDIs (nHDIs) of the same genes according to transcript expression and drug responses in various cancer type cell lines. Collectively, these results indicated the complex properties of HDIs per gene identified by cancer type-based isoform-isoform co-expression networks and showed the potential of HDIs as novel therapeutic targets for cancer treatment.

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer.

Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options.

[Study on intrapartum service model during normal labor].

OBJECTIVE: To study the availability of humanized service and healthy birth and it's effect on maternal and neonatal outcomes. METHODS: A multicenteral prospective randomized control study was carried out in 9 maternity hospitals from Nov. 2000 to June 2001. 6,758 laboring women were randomly divided into study group and control group. In study group (n = 3,437), midwives accompany laboring women in whole course of birth until two hours after delivery. According WHO "Monitoring rules for normal birth" medical staff support the mothers in physiological, psychological and physical aspects. In control group (n = 3,321) mothers receive traditional management. Midwives visit and check the mothers discoutinually. In two groups husbands can company laboring women according women's requirement. A questionnaire will be filled on the second day after birth. RESULTS: In study group the spontaneous delivery rate was significant higher than that of control group (85.5% vs 66.0%, P < 0.01). The cesarean section rate, postpartum hemorrhage rate, neonatal asphyxia rate and neonatal morbidity were marked lower in study group than those of control group (P < 0.01 and P < 0.05). CONCLUSIONS: Appropriate mode of intrapartum care can decrease the cesarean section rate and promote the vaginal delivery, also it can improve the maternal and neonatal outcomes.

Weakening density dependence from climate change and agricultural intensification triggers pest outbreaks: a 37-year observation of cotton bollworms.

Understanding drivers of population fluctuation, especially for agricultural pests, is central to the provision of agro-ecosystem services. Here, we examine the role of endogenous density dependence and exogenous factors of climate and human activity in regulating the 37-year population dynamics of an important agricultural insect pest, the cotton bollworm (Helicoverpa armigera), in North China from 1975 to 2011. Quantitative time-series analysis provided strong evidence explaining long-term population dynamics of the cotton bollworm and its driving factors. Rising temperature and declining rainfall exacerbated the effect of agricultural intensification on continuously weakening the negative density dependence in regulating the population dynamics of cotton bollworms. Consequently, ongoing climate change and agricultural intensification unleashed the tightly regulated pest population and triggered the regional outbreak of H. armigera in 1992. Although the negative density dependence can effectively regulate the population change rate to fluctuate around zero at stable equilibrium levels before and after outbreak in the 1992, the population equilibrium jumped to a higher density level with apparently larger amplitudes after the outbreak. The results highlight the possibility for exogenous factors to induce pest outbreaks and alter the population regulating mechanism of negative density dependence and, thus, the stable equilibrium of the pest population, often to a higher level, posing considerable risks to the provision of agro-ecosystem services and regional food security. Efficient and timely measures of pest management in the era of Anthropocene should target the strengthening and revival of weakening density dependence caused by climate change and human activities.