Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States.

PURPOSE: Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors. METHODS: A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose-response relationship between serum 25(OH)D concentrations and mortality. RESULTS: The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56-0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32-0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45-0.99). RCS curves revealed "L-shaped" associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009). CONCLUSION: Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Sucking lollipop after awakening from sevoflurane anesthesia reduces the degree of emergence agitation in children undergoing ambulatory surgery: A prospective randomized controlled trial.

BACKGROUND: Emergence agitation (EA) is a common complication in pediatric anesthesia, especially in preschool children maintained by sevoflurane, with incidence ranging up to 80%. The purpose of the study was to determine whether sucking lollipop after awakening from sevoflurane anesthesia reduced the degree of EA in children undergoing ambulatory surgery. METHODS: In this prospective study, 40 children aged 2 to 6 years scheduled for ambulatory surgery with sevoflurane were enrolled. They were randomly allocated to 1 of 2 groups after evaluating baseline EA levels using the pediatric anesthesia emergence delirium (PAED) scale immediately after awakening from general anesthesia: group L (sucking lollipop) or group C (control group, without sucking lollipop). The primary outcome was the overall PAED score after intervention. Pain score, parental satisfaction, the incidence of propofol rescue and negative postoperative behavioral changes (NPOBCs) were assessed. RESULTS: The overall PAED score after intervention was significantly lower in Group L compared with Group C, with an estimated difference of -1.857 (95% CI, -2.884 to -0.831; P < .001) using generalized estimating equations. However, no significant intergroup differences were observed in the pain score, parental satisfaction, the incidence of propofol rescue and NPOBCs. CONCLUSIONS: Sucking lollipop after awakening from sevoflurane anesthesia reduced the degree EA in children undergoing ambulatory surgery.

Gold Nanoparticles Enhance the Ability of Radiotherapy to Induce Immunogenic Cell Death in Glioblastoma.

Background: Radiation therapy (RT) is commonly used to treat glioblastoma, but its immunomodulatory effect on tumors, through mechanisms such as immunogenic cell death (ICD), is relatively weak. Gold nanoparticles (AuNPs) have been suggested as potential radio-sensitizers, but it is unclear if they can enhance radiation-induced ICD. This study aimed to investigate the potential of AuNPs to improve the effectiveness of radiation-induced ICD. Methods: G422 cells were treated with a combination of AuNPs and RT to induce cell death. Various assays were conducted to assess cell death, surface expression of CRT, and release of HMGB1 and ATP. In vitro co-culture experiments with bone marrow-derived dendritic cells (BMDCs) were performed to analyze the immunogenicity of dying cancer cells. Flow cytometry was used to measure the maturation rate of BMDCs. An in vivo mouse tumor prophylactic vaccination model was employed to assess immunogenicity. Results: The study findings presented here confirm that the combination of radiotherapy (RT) with AuNPs can induce a stronger ICD effect on glioblastoma cells compared to using RT alone. Specifically, treatment with AuNPs combined with RT resulted in the emission of crucial damage-associated molecular patterns (DAMPs) such as CRT, HMGB1 (479.41±165.34pg/mL vs 216.04±178.16 pg/mL, *P<0.05) and ATP (The release of ATP in the AuNPs + RT group was 1.2 times higher than in the RT group, *P<0.05). The proportion of BMDC maturation rate was higher in the group treated with AuNPs and RT compared to the group treated with RT alone. (32.53±0.52% vs 25.03±0.28%,***P < 0.001). In the tumor vaccine experiment, dying tumor cells treated with AuNPs and RT effectively inhibited tumor growth in mice when exposed to living tumor cells. Conclusion: These results indicate that AuNPs have the ability to enhance RT-induced ICD.

Intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during cesarean section: a prospective, double-blinded, randomized trial for ED50 determination using an up-down sequential allocation method.

BACKGROUND: Intrathecal dexmedetomidine, as an adjuvant to local anesthetics, has been reported to improve the quality of spinal anesthesia and reduce the required local anesthetic dose. However, the optimal dosage regimen for intrathecal dexmedetomidine combined with plain ropivacaine for cesarean section (CS) remains undetermined. The present study aimed to determine the median effective dose (ED50) of intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during CS. METHODS: Sixty parturients undergoing CS were randomly assigned to either group: plain ropivacaine 8 mg (Group Rop8) or plain ropivacaine 10 mg (Group Rop10). The initial dosage of intrathecal dexmedetomidine in each group was 5 µg. The effective dose was defined as a bilateral sensory block at the level of T6 or above to pinprick attained within 10 min after intrathecal injection, without the need for supplementary intraoperative epidural anesthesia. Effective or ineffective responses were determined, followed by a 1 µg increment or decrement in the dose of intrathecal dexmedetomidine for the next parturient using up-down sequential allocation. ED50 were calculated using probit regression. RESULTS: The ED50 of intrathecal dexmedetomidine with plain ropivacaine was 5.9 µg (95% confidence interval [CI], 4.9-7.4 µg) in Group Rop8 and 3.1 µg (95% CI, 0.1-4.8 µg) in Group Rop10 (P < 0.05). Hemodynamic stability, side effects, patient satisfaction and neonatal outcomes were comparable between the two groups. CONCLUSIONS: The present data suggested that the ED50 of intrathecal dexmedetomidine as an adjuvant to 8 mg and 10 mg plain ropivacaine in spinal anesthesia during cesarean section was approximately 6 µg and 3 µg, respectively. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2200055928.

Association of serum total 25-hydroxy-vitamin D concentration and risk of all-cause, cardiovascular and malignancies-specific mortality in patients with hyperlipidemia in the United States.

Background: Vitamin D (VD) plays an important role in decreasing the risk of adverse events for various metabolic diseases. However, for patients with hyperlipidemia, the relationship between the main VD storage within the body known as serum 25-hydroxy-VD [25(OH)VD] and the risk of all-cause, cardiovascular and malignancies-specific mortality is still unclear. Materials and methods: A total of 6740 participants above the age of 20 years with hyperlipidemia who completed the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 and were followed up until 2019 were included in the study. The weighted Cox proportional hazards regression model and weighted competing risk regression model were used to evaluate the risk for all-cause, cardiovascular and malignancy-related mortality in relation to the serum 25(OH)VD. The model was adjusted according to age, gender, race, body mass index, lipids status, medication usage, the Charlson comorbidity index and healthy eating index. The last restricted cubic spline (RCS) method was used to present the relationship between hazard ratios (HR) associated with diverse cause-specified modalities and the serum 25(OH)VD levels. Results: Serum 25(OH)VD was identified as an independent factor for mortality. Lower serum 25(OH)VD under the threshold of 25.6 and 25.2 ng/ml were significantly associated with a higher risk for all-cause and cardiovascular mortalities, respectively. However, no association was found between malignancy-specific mortality and serum 25(OH)VD. Conclusion: Serum 25(OH)VD were identified as an independent factor associated with risks of all-cause and cardiovascular mortalities in patient with hyperlipidemia. Moreover, lower serum 25(OH)VD than 25.6 and 25.2 ng/mL were, respectively, associated with a gradual increase in a risk for all-cause and cardiovascular mortality in patients with hyperlipidemia, and therefore regular monitoring of VD levels and correction of VD deficiency is recommended in those patients.

Programmed Intermittent Epidural Bolus in Comparison with Continuous Epidural Infusion for Uterine Contraction Pain Relief After Cesarean Section: A Randomized, Double-Blind Clinical Trial.

Purpose: Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after cesarean section remains unknown. Patients and Methods: Parturients scheduled for cesarean section were recruited for the study. At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL·h-1) or CEI (6 mL·h-1) of 0.1% ropivacaine. The primary outcome was the uterine contraction pain assessed with visual analog scale (VAS-U) at the postoperative 36 h. Secondary outcomes included incision pain at the rest (VAS-R) and in the movement-evoked (VAS-P), and lower extremity motor block (defined as Bromage score > 0). The whole profile of VAS scores between groups was analyzed using linear mixed model. When significant differences were found, the pairwise comparison was done with the Mann Whitney U-test followed by Bonferroni correction. Results: One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). VAS-U at the postoperative 36 h in the PIEB group was lower than in the CEI group (Bonferroni-adjusted P < 0.01). The linear mixed model indicated that VAS-U, VAS-R and VAS-P were lower in the PIEB group compared with the CEI group (all P < 0.01). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P < 0.05). No differences of adverse events such as hypotension and urinary retention were observed between the two groups. Conclusion: Programmed intermittent epidural bolus provides more effective uterine contraction and incision pain relief and less motor block after cesarean section than continuous epidural infusion without an increased risk of urinary retention and blood pressure instability.

Physical and Numerical Simulations on Mechanical Properties of a Prefabricated Underground Utility Tunnel.

The "U-shaped ferrule joint bars connections" have a stable mechanical property, requiring a low level of construction accuracy and a relatively simple connection process, which significantly increase the construction speed. Based on the "U-shaped ferrule joint bars connections" technology, a new type of prefabricated concrete underground utility tunnel was proposed. This prefabricated technology realizes a formwork-free construction and vertical support-free assembly of the top plate on site. Through the full-scale model static test and numerical analyses, the mechanical properties, i.e., the crack development law and bearing capacity, were systematically investigated to validate the effectiveness of the "U-shaped ferrule joint bars connections". The test results indicated that the performance of the "U-shaped ferrule joint bars connections" is reliable. During the loading process, the prefabricated utility tunnel experienced three stages, i.e., cracking, stiffness degradation, and ultimate failure. The numerical analysis results correlated with the test results well. The simulation results showed that the bearing capacities of the prefabricated underground utility tunnel and the cast-in-place utility tunnel were similar. The longitudinal joint connections of the prefabricated utility tunnel allow the structure as an integration to maintain favourable mechanical properties.

Efficacy of Anlotinib for the Treatment of Angiosarcoma of the Face and Neck: A Case Report.

Angiosarcoma of the face and neck is a rare soft tissue sarcoma with a high degree of malignancy. The current treatment methods mainly rely on a combination of surgery and radiotherapy and/or chemotherapy. However, the options for drug treatment are very limited and surgery can be difficult to carry out due to the location of the tumor, so the efficacy of first-line drugs needs to be constantly explored. A case of angiosarcoma of the head and face diagnosed by biopsy is reported here. The patient received an oral anlotinib hydrochloride capsule once a day (12 mg on days 1 - 14/1 week off for a 21-day cycle) due to the difficulty of surgery. Until now (April, 2020), after 10 months of treatment, the patient's scalp and facial lesions have gradually reduced and the partial response and progression-free survival of this patient were good, with moderate or tolerable adverse events. This approach provides a new approach for the clinical treatment of malignant angiosarcoma of the face and neck with anlotinib as first-line therapy.

Estimating the risk of developing secondary hematologic malignancies in patients with T1/T2 prostate cancer undergoing diverse treatment modalities: A large population-based study.

BACKGROUND: Patients with prostate cancer (PC) are at a high risk of developing secondary hematologic malignancies (SHMs) after radiation therapy (RT), while no study has assessed the relationship of different treatment modalities with the occurrence of SHMs after PC at early stage. This study aimed to investigate the risks of developing SHMs in patients with T1/T2 PC undergoing different treatment modalities. METHODS: Patients with T1/T2 PC were identified from the Surveillance, Epidemiology, and End Results database. Competing risk regression (CRR) model was performed to evaluate the hazard ratios (HRs) of developing SHMs. As SHMs scarcely occur, the relative risk (RR) analysis was employed to compare the risks of different treatment modalities associating with the development of SHMs. RESULTS: The CRR analysis showed that undergoing RT was associated with a higher risk of developing SHMs (external beam radiation therapy [EBRT]: HR = 1.21, 95% confidence interval [CI]: 1.10-1.34; radioactive implant [RI]: HR = 1.20, 95% CI: 1.06-1.36). As for different types of SHMs, EBRT, and RI were correlated with decreased risks of developing CLL (RR = 0.67, 0.72; 95% CI: 0.53-0.85, 0.54-0.96, respectively), but with the increased risks of developing NHL (RR = 1.18, 1.23; 95% CI: 1.02-1.35, 1.05-1.44, respectively); EBRT also showed increased risks of developing acute/ chronic myeloid leukemia (AML/CML, RR = 1.54, 1.56; 95% CI: 1.16-2.03,1.05-2.33, respectively); No increased risk of developing SHMs was detected in patients who only underwent prostatectomy. CONCLUSIONS: Although RT was found to be associated with the increased risks of developing SHMs in patients with T1/T2 PC, this finding cannot be extended to diverse types of SHMs. RT was correlated with the increased risks of the development of NHL, AML, and CML, but with the decreased risk of developing CLL. Prostatectomy did not increase the risk of developing SHMs.

Genomic variation, origin tracing, and vaccine development of SARS-CoV-2: A systematic review.

COVID-19 has spread globally to over 200 countries with more than 40 million confirmed cases and one million deaths as of November 1, 2020. The SARS-CoV-2 virus, leading to COVID-19, shows extremely high rates of infectivity and replication, and can result in pneumonia, acute respiratory distress, or even mortality. SARS-CoV-2 has been found to continue to rapidly evolve, with several genomic variants emerging in different regions throughout the world. In addition, despite intensive study of the spike protein, its origin, and molecular mechanisms in mediating host invasion are still only partially resolved. Finally, the repertoire of drugs for COVID-19 treatment is still limited, with several candidates still under clinical trial and no effective therapeutic yet reported. Although vaccines based on either DNA/mRNA or protein have been deployed, their efficacy against emerging variants requires ongoing study, with multivalent vaccines supplanting the first-generation vaccines due to their low efficacy against new strains. Here, we provide a systematic review of studies on the epidemiology, immunological pathogenesis, molecular mechanisms, and structural biology, as well as approaches for drug or vaccine development for SARS-CoV-2.

A Novel XGBoost Method to Infer the Primary Lesion of 20 Solid Tumor Types From Gene Expression Data.

PURPOSE: Establish a suitable machine learning model to identify its primary lesions for primary metastatic tumors in an integrated learning approach, making it more accurate to improve primary lesions' diagnostic efficiency. METHODS: After deleting the features whose expression level is lower than the threshold, we use two methods to perform feature selection and use XGBoost for classification. After the optimal model is selected through 10-fold cross-validation, it is verified on an independent test set. RESULTS: Selecting features with around 800 genes for training, the R 2-score of a 10-fold CV of training data can reach 96.38%, and the R 2-score of test data can reach 83.3%. CONCLUSION: These findings suggest that by combining tumor data with machine learning methods, each cancer has its corresponding classification accuracy, which can be used to predict primary metastatic tumors' location. The machine-learning-based method can be used as an orthogonal diagnostic method to judge the machine learning model processing and clinical actual pathological conditions.

Identification and Validation of Efficacy of Immunological Therapy for Lung Cancer From Histopathological Images Based on Deep Learning.

Cancer immunotherapy, as a novel treatment against cancer metastasis and recurrence, has brought a significantly promising and effective therapy for cancer treatments. At present, programmed death 1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) treatment for lung cancer is primarily recognized as an immune checkpoint inhibitor (ICI) to play an anti-tumor effect; however, it remains uncertain regarding of its efficacy though. Thereafter, tumor mutation burden (TMB) was recognized as a high-potential to be a predictive marker for the immune therapy, but it is invasive and costly. Therefore, discovering more immune-related biomarkers that have a guiding role in immunotherapy is a crucial step in the development of immunotherapy. In our study, we proposed a deep convolutional neural network (CNN)-based framework, DeepLRHE, which can efficiently analyze immunological stained pathological images of lung cancer tissues, as well as to identify and explore pathogenesis which can be used for immunological treatment in clinical field. In this study, we used 180 whole slice images (WSIs) of lung cancer downloaded from TCGA which was model training and validation. After two cross-validation used for this model, we compared with the area under the curve (AUC) of multiple mutant genes, TP53 had highest AUC, which reached 0.87, and EGFR, DNMT3A, PBRM1, STK11 also reached ranged from 0.71 to 0.84. The study results showed that the deep learning can used to assist health professionals for target-therapy as well as immunotherapies, therefore to improve the disease prognosis.

Competing risk analysis of cardiovascular/cerebrovascular death in T1/2 kidney cancer: a SEER database analysis.

BACKGROUND: Kidney cancer (KC) is associated with cardiovascular regulation disorder and easily leads to cardiovascular and cerebrovascular death (CCD), which is one of the major causes of death in patients with KC, especially those with T1/2 status. However, few studies have treated CCD as an independent outcome for analysis. We aimed to identify and evaluate the key factors associated with CCD in patients with T1/2 KC by competing risk analysis and compared these risk factors with those associated with kidney cancer-specific death (KCD) to offer some information for clinical management. METHODS: A total of 45,117 patients diagnosed with first primary KC in T1/2 status were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into the CCD group (n = 3087), KCD group (n = 3212), other events group (n = 6312) or alive group (n = 32,506). Patients' characteristics were estimated for their association with CCD or KCD by a competing risk model. Pearson's correlation coefficient and variance inflation factor (VIF) were used to detect collinearity between variables. Factors significantly correlated with CCD or KCD were used to create forest plots to compare their differences. RESULTS: The competing risk analysis showed that age at diagnosis, race, AJCC T/N status, radiation therapy, chemotherapy and scope of lymph node represented different relationships to CCD than to KCD. In detail, age at diagnosis (over 74/1-50: HR = 9.525, 95% CI: 8.049-11.273), race (white/black: HR = 1.475, 95% CI: 1.334-1.632), AJCC T status (T2/T1: HR = 0.847, 95% CI: 0.758-0.946) and chemotherapy (received/unreceived: HR = 0.574, 95% CI: 0.347-0.949) were correlated significantly with CCD; age at diagnosis (over 74/1-50: HR = 3.205, 95% CI: 2.814-3.650), AJCC T/N status (T2/T1: HR = 2.259, 95% CI: 2.081-2.451 and N1/N0:HR = 3.347, 95% CI: 2.698-4.152), radiation therapy (received/unreceived: HR = 2.552, 95% CI: 1.946-3.346), chemotherapy (received/unreceived: HR = 2.896, 95% CI: 2.342-3.581) and scope of lymph nodes (1-3 regional lymph nodes removed/none: HR = 1.378, 95% CI: 1.206-1.575) were correlated significantly with KCD. CONCLUSIONS: We found that age at diagnosis, race, AJCC T status and chemotherapy as the independent risk factors associated with CCD were different from those associated with KCD.

A Machine Learning Approach for Tracing Tumor Original Sites With Gene Expression Profiles.

Some carcinomas show that one or more metastatic sites appear with unknown origins. The identification of primary or metastatic tumor tissues is crucial for physicians to develop precise treatment plans for patients. With unknown primary origin sites, it is challenging to design specific plans for patients. Usually, those patients receive broad-spectrum chemotherapy, while still having poor prognosis though. Machine learning has been widely used and already achieved significant advantages in clinical practices. In this study, we classify and predict a large number of tumor samples with uncertain origins by applying the random forest and Naive Bayesian algorithms. We use the precision, recall, and other measurements to evaluate the performance of our approach. The results have showed that the prediction accuracy of this method was 90.4 for 7,713 samples. The accuracy was 80% for 20 metastatic tumors samples. In addition, the 10-fold cross-validation is used to evaluate the accuracy of classification, which reaches 91%.

DeepLRHE: A Deep Convolutional Neural Network Framework to Evaluate the Risk of Lung Cancer Recurrence and Metastasis From Histopathology Images.

It is critical for patients who cannot undergo eradicable surgery to predict the risk of lung cancer recurrence and metastasis; therefore, the physicians can design the appropriate adjuvant therapy plan. However, traditional circulating tumor cell (CTC) detection or next-generation sequencing (NGS)-based methods are usually expensive and time-inefficient, which urge the need for more efficient computational models. In this study, we have established a convolutional neural network (CNN) framework called DeepLRHE to predict the recurrence risk of lung cancer by analyzing histopathological images of patients. The steps for using DeepLRHE include automatic tumor region identification, image normalization, biomarker identification, and sample classification. In practice, we used 110 lung cancer samples downloaded from The Cancer Genome Atlas (TCGA) database to train and validate our CNN model and 101 samples as independent test dataset. The area under the receiver operating characteristic (ROC) curve (AUC) for test dataset was 0.79, suggesting a relatively good prediction performance. Our study demonstrates that the features extracted from histopathological images could be well used to predict lung cancer recurrence after surgical resection and help classify patients who should receive additional adjuvant therapy.

Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma.

Sorafenib is the first FDA-approved therapeutic drug for molecular target medication on advanced-stage hepatocellular carcinoma. It is reported that sorafenib could improve the survival of progression-free patients for 4 to 6 months; however, most of the patients developed drug resistance. Thus, it is critical to reveal the biological mechanisms behind sorafenib resistance. In this study, a sorafenib-resistant model was developed by exposing HepG2 cells to sorafenib with gradient increasing concentration, and the resistance-related genes were screened by microarray. Real-time qPCR was used to validate selected gene expression of the resistance model, and lentivirus vector-mediated RNA interference was applied for specific gene knockdown. In addition, high-throughput High Celigo Select (HCS) and flow cytometry were used to measure the effect on cellular proliferation and apoptosis. As a result, our study established a sorafenib-resistant model with IC50 of 9.988 µM. The Affymetrix expression profile of the sorafenib-resistant model showed 35 resistant-related genes, and 91.4% of the resistant genes showed upregulation in HepG2 resistance cells. In addition, 20 genes were knocked down to measure cell proliferation, and MAP4K3 with high proliferation inhibiting phenotype was chosen for further study. Meanwhile, the HCS results revealed that shMAP4K3 transfection could downregulate resistant cell proliferation, and the flow cytometry results showed that cell apoptosis was significantly increased in the MAP4K3 knockdown group. In summary, MAP4K3 is a novel molecular marker for improving the drug sensitivity of sorafenib treatment in hepatocellular carcinoma.

Gene Coexpression Network and Module Analysis across 52 Human Tissues.

Gene coexpression analysis is widely used to infer gene modules associated with diseases and other clinical traits. However, a systematic view and comparison of gene coexpression networks and modules across a cohort of tissues are more or less ignored. In this study, we first construct gene coexpression networks and modules of 52 GTEx tissues and cell lines. The network modules are enriched in many tissue-common functions like organelle membrane and tissue-specific functions. We then study the correlation of tissues from the network point of view. As a result, the network modules of most tissues are significantly correlated, indicating a general similar network pattern across tissues. However, the level of similarity among the tissues is different. The tissues closing in a physical location seem to be more similar in their coexpression networks. For example, the two adjacent tissues fallopian tube and bladder have the highest Fisher's exact test p value 8.54E-291 among all tissue pairs. It is known that immune-associated modules are frequently identified in coexperssion modules. In this study, we found immune modules in many tissues like liver, kidney cortex, lung, uterus, adipose subcutaneous, and adipose visceral omentum. However, not all tissues have immune-associated modules, for example, brain cerebellum. Finally, by the clique analysis, we identify the largest clique of modules, in which the genes in each module are significantly overlapped with those in other modules. As a result, we are able to find a clique of size 40 (out of 52 tissues), indicating a strong correlation of modules across tissues. It is not surprising that the 40 modules are most commonly enriched in immune-related functions.

[Effects of propofol sedation on psychological stress in surgical patients under epidural].

OBJECTIVE: To explore the effects of propofol sedation on psychological stress in patients undergoing surgery under epidural anesthesia. METHODS: Sixty patients scheduled to undergo elective ileostomy closure under epidural anesthesia were randomized into propofol sedation group and control group (n=30). The patients in the sedation group received a loading dose of propofol of 0.6 mg·kg- 1· h- 1 followed by a maintenance dose with continuous infusion of 3 mg·kg- 1· h- 1 given after the Observer's Assessment of Alertness/Sedation (OAA/S) score reached 2-3. An equivalent volume of normal saline was administered in patients in the control group. The patients' preoperative and intraoperative anxiety scores were assessed with the State Anxiety Inventory (SAI) on the day before and on the first day after the surgery, respectively. The mean blood pressure (MBP), heart rate (HR), SpO2, OAA/S, and the indicators of psychological stress of brain functional state of the patients (including the wavelet index [WLi], anxiety index [ANXi], comfortable index [CFi] and pain index [Pi]) were recorded at 5 min after entering the operating room (T0), at the time of lumbar puncture (T1) and change to supine position after the puncture (T2), at 20 s (T3), 40 s (T4), and 60 s (T5) after intravenous administration, and at 2 min (T6), 4 min (T5), 6 min (T8), 8 min (T9), 10 min (T10) and 40 min (T11) after skin incision. The patient's satisfaction with anesthesia was assessed with the Visual Analog Scale (VAS) score on the first day after the operation. Serum cortisol level was measured before anesthesia and at the end of operation to calculate the changes in cortisol level. RESULTS: The two groups of patients were comparable for preoperative SAI scores (P>0.05); The patients in the sedation group appeared to have lower intraoprative SAI scores, but this difference was not statistically significant (P=0.05). MBP, HR, and SpO2 at the time points from T6 to T10 and OAA/S, WLi, ANXi, CFi, and Pi at the time points from T6 to T11 were significantly lower in the sedation group (all P < 0.05), and these parameters were not significantly different between the two groups at the other time points (all P>0.05). The patient satisfaction scores were significantly higher in the sedation group (Z=2.07, P < 0.05). Compared with the preoperative levels, serum cortisol level at the end of the operation was increased in the sedation group but lowered in the control group, and the variations of serum cortisol level differed significantly between the two groups (t=4.75, P < 0.01). CONCLUSIONS: Intraoperative propofol sedation can alleviate the patients' anxiety, improve the comfort level, and lessen physiological stress during surgeries under epidural anesthesia.

Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent Hsp90 C-terminal inhibitors.

In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding pocket, a novobiocin derivative based ROCS model was constructed for virtual screening. Compound 13 was identified as the lead compound and then systematical structure activity relationship (SAR) study was conducted. These efforts led to compound 69, which exhibited potent anti-proliferative activities against MCF7 and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69 exhibited potent tumor growth inhibition and anti-metastasis effect. Compound 69 as a potent antitumor agent targeting the Hsp90 C-terminal is worthy of further pre-clinical study.

Design, synthesis, and evaluation of benzofuran derivatives as novel anti-pancreatic carcinoma agents via interfering the hypoxia environment by targeting HIF-1α pathway.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common type of pancreatic cancer, and has still been the medicinal mystery. New drugs and treatment strategies are urgently needed. In this study, 32 benzofuran derivatives are designed, synthesized and evaluated as potential agents against the pancreatic cancer. Among them, compound 9o with the best physicochemical and pharmacokinetic properties exhibited excellent cytotoxicity against many tumor cell lines. In vivo study showed that compound 9o dramatically suppressed the tumor growth of nude mice. Furthermore, compound 9o could affect the hypoxia environment through Hif-1α/VEGF pathway, resulting in the anti-angiogenic activity. These studies indicated that compound 9o was a promising candidate for the treatment of PDAC, deserving further studies.