DIRMC: a database of immunotherapy-related molecular characteristics.

Cancer immunotherapy has brought about a revolutionary breakthrough in the field of cancer treatment. Immunotherapy has changed the treatment landscape for a variety of solid and hematologic malignancies. To assist researchers in efficiently uncovering valuable information related to cancer immunotherapy, we have presented a manually curated comprehensive database called DIRMC, which focuses on molecular features involved in cancer immunotherapy. All the content was collected manually from published literature, authoritative clinical trial data submitted by clinicians, some databases for drug target prediction such as DrugBank, and some experimentally confirmed high-throughput data sets for the characterization of immune-related molecular interactions in cancer, such as a curated database of T-cell receptor sequences with known antigen specificity (VDJdb), a pathology-associated TCR database (McPAS-TCR) et al. By constructing a fully connected functional network, ranging from cancer-related gene mutations to target genes to translated target proteins to protein regions or sites that may specifically affect protein function, we aim to comprehensively characterize molecular features related to cancer immunotherapy. We have developed the scoring criteria to assess the reliability of each MHC-peptide-T-cell receptor (TCR) interaction item to provide a reference for users. The database provides a user-friendly interface to browse and retrieve data by genes, target proteins, diseases and more. DIRMC also provides a download and submission page for researchers to access data of interest for further investigation or submit new interactions related to cancer immunotherapy targets. Furthermore, DIRMC provides a graphical interface to help users predict the binding affinity between their own peptide of interest and MHC or TCR. This database will provide researchers with a one-stop resource to understand cancer immunotherapy-related targets as well as data on MHC-peptide-TCR interactions. It aims to offer reliable molecular characteristics support for both the analysis of the current status of cancer immunotherapy and the development of new immunotherapy. DIRMC is available at http://www.dirmc.tech/. Database URL: http://www.dirmc.tech/.

An analytical study of employee loyalty and corporate culture satisfaction assessment based on sentiment analysis.

As an important factor related to the interests of enterprises, the attitude and behavior of employees are related to the company's survival and the realization of business objectives. However, in recent years, with the rapid development of emerging industries and industry changes, the turnover rate of employees in the whole enterprise has been greatly improved. Frequent turnover of personnel will have a great impact on the stability of the company, the competitiveness of the enterprise, and the operating cost. Employee loyalty and corporate culture satisfaction assessment is the core of sustainable corporate development, but most of the traditional analysis studies are based on the performance approach, using employee overtime, employee achievement, and company effectiveness as data sources, the former performance data is only a side view of the company's situation, the latter as the data source of this study is a one-sided and involute form, and the data is not stable. Therefore, this paper proposes an analysis of employee loyalty and corporate culture satisfaction assessment based on sentiment analysis, using association rules and sentiment lexicons from anonymous employee evaluations to analyze the actual data.

Structure elucidation and antimicrobial activities of five compounds from Artemisia integrifolia L.

A new compound, integracid (1), together with four known compounds were isolated from the dichloromethane (CH2Cl2) extract from Artemisia integrifolia L. The structures of compounds (1-5) were elucidated by spectroscopic methods, including ultraviolet, infrared (IR), high resolution-electrospray ionization-mass spectrometry (HR-ESI-MS) and extensive one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) techniques, and by comparison with data reported in the references. Antibacterial activities of the compounds were evaluated against various bacteria.

Ganglioglioma: a clinicopathological study of 19 cases / 临床与实验病理学杂志

Purpose To study the clinicopathologic features of ganglioglioma. Methods The clinicopathologic data of the cases pathologically diagnosed as ganglioglioma that underwent resection of epileptic focus were retrospectively analyzed. Results In the 19 cases studied, the mean onset age was 9.1 years, and the duration of disease was 9.3 years. MRI images showed abnormal signals. The majority of the site was temporal lobe (14/19, 73.7％). The tumors showed heterogeneity and often accompanied by focal cortical dysplasias (13/19, 68.4％). Immunohistochemical staining showed CD34 positive in 18 cases, Nestin positive in 16 cases, and BRAF-V600E positive in 6 case. The positive expression rate of CD34 and Nestin did not have significant differences. Conclusion The diagnosis of ganglioglioma relies on pathological observations combined with clinical features and neuroradiological examinations. Differential diagnosis should be done from other tumors or cortical dysplasia. Immunohistochemical staining of CD34 and Nestin can help diagnosis.

Interactions between SirT1 and STAT3 in the retinal pigmented epithelium cell / 眼科新进展

Objective To investigate the interactions between histone deacetylas-1 (silent information regulator of transcription 1,SirT1) and signal transducer and activator of transcription 3 (STAT3) following exposure to oxidative stress of retinal pigmented epithelium (RPE) cells through gene knockout and overexpression techniques.Methods RPE cell line was cultured in vitro,followed by addition of H2O2 for inducing oxidative stress.The targeting knockout strategy (siRNA/shRNA) was used for silencing SirT1/STAT3 gene and lentiviral vectors (pRC/CMV STAT3 and PCRC/CMV) were transfected to RPE cells.RT-qPCR and Western blot were used to detect the expression of SirT1/STAT3 due to gene knockout and overexpression and deeply analyze the effects of SirT1/STAT3 on RPE cells exposed to oxidative stress.Results SirT1 activator (resveratrol) significantly reduced the expression of STAT3 mRNA to (3.0 ± 0.2) (P =0.048);and after SifT1 knockout,the expression of STAT3 mRNA in RPE cells was significantly increased to (6.9 ± 1.1) (P =0.025).During the oxidative stress of RPE cells after SifT1 knockout,the expression of STAT3 and phosphorylated STAT3 protein were significantly increased to 0.990 ±0.031 and 0.544 ±0.019,respectively (P =0.000,0.003).With the condition of oxidative stress,the over-expression of STAT3 reduced the SirT1 mRNA expression to 0.42 ± 0.16 (P =0.022),but SifT1 mRNA expression was significantly increased to 2.8 ±0.85 (P =0.015) during STAT3 knockdown.Conclusion SifT1 has a negative effect on the regulation of STAT3 expression during oxidative stress,which suggests that there is an equilibrium mechanism between SirT1 and STAT3 against oxidative stress.

Differential effects of etomidate and its pyrrole analogue carboetomidate on the adrenocortical and cytokine responses to endotoxemia.

OBJECTIVE: We developed a novel pyrrole analog of etomidate, (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), which retains etomidate's desirable anesthetic and hemodynamic properties but lacks its potent inhibitory affect on adrenocorticotropic hormone-stimulated steroid synthesis. The objective of this study was to test the hypothesis that in contrast to etomidate, carboetomidate neither suppresses the adrenocortical response to endotoxemia nor enhances the accompanying production of proinflammatory cytokines. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: For both single and multiple anesthetic dose studies, rats were injected with Escherichia coli lipopolysaccharide immediately followed by a hypnotic dose of etomidate, carboetomidate, or vehicle alone (dimethyl sulfoxide) as a control. For single-dose studies, no additional anesthetic (or vehicle) was administered. For multiple anesthetic dose studies, additional doses of anesthetic (or vehicle) were administered every 15 mins for a total of eight anesthetic (or vehicle) doses. MEASUREMENTS AND MAIN RESULTS: Plasma adrenocorticotropic hormone, corticosterone, and cytokine concentrations were measured before lipopolysaccharide administration and intermittently throughout the 5-hr experiment. In single anesthetic dose studies, plasma adrenocorticotropic hormone and cytokine concentrations were not different at any time point among the etomidate, carboetomidate, and vehicle groups, whereas plasma corticosterone concentrations were briefly (60-120 mins) reduced in the etomidate group. In multiple anesthetic dose studies, plasma corticosterone concentrations were persistently lower and peak plasma interleukin-1ß and interleukin-6 concentrations were higher in the etomidate group vs. the carboetomidate and control groups. Peak plasma interleukin-10 concentrations were similarly elevated in the etomidate and carboetomidate groups vs. the control group. CONCLUSIONS: Compared with etomidate, carboetomidate produces less suppression of adrenocortical function and smaller increases in proinflammatory cytokine production in an endotoxemia model of sepsis. These findings suggest that carboetomidate could be a useful alternative to etomidate for maintaining anesthesia for a prolonged period of time in patients with sepsis.

In vivo and in vitro pharmacological studies of methoxycarbonyl-carboetomidate.

BACKGROUND: We previously developed 2 etomidate analogs that retain etomidate's favorable hemodynamic properties but whose adrenocortical effects are reduced in duration or magnitude. Methoxycarbonyl (MOC)-etomidate is rapidly metabolized and ultrashort acting whereas (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) does not potently inhibit 11ß-hydroxylase. We hypothesized that MOC-etomidate's labile ester could be incorporated into carboetomidate to produce a new agent that possesses favorable properties individually found in each agent. We describe the synthesis and pharmacology of MOC-(R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (MOC-carboetomidate), a "soft" analog of carboetomidate. METHODS: MOC-carboetomidate's octanol:water partition coefficient was determined chromatographically and compared with those of etomidate, carboetomidate, and MOC-etomidate. MOC-carboetomidate's 50% effective concentration (EC(50)) and 50% effective dose for loss of righting reflexes (LORR) were measured in tadpoles and rats, respectively. Its effect on γ-aminobutyric acid A (GABA(A)) receptor function was assessed using 2-microelectrode voltage clamp electrophysiological techniques and its metabolic stability was determined in pooled rat blood using high performance liquid chromatography. Its duration of action and effects on arterial blood pressure and adrenocortical function were assessed in rats. RESULTS: MOC-carboetomidate's octanol:water partition coefficient was 3300 ± 280, whereas those for etomidate, carboetomidate, and MOC-etomidate were 800 ± 180, 15,000 ± 3700, and 190 ± 25, respectively. MOC-carboetomidate's EC(50) for LORR in tadpoles was 9 ± 1 µM and its EC(50) for LORR in rats was 13 ± 5 mg/kg. At 13 µM, MOC-carboetomidate enhanced GABA(A) receptor currents by 400% ± 100%. Its metabolic half-life in pooled rat blood was 1.3 min. The slope of a plot of the duration of LORR in rats versus the logarithm of the hypnotic dose was significantly shallower for MOC-carboetomidate than for carboetomidate (4 ± 1 vs 15 ± 3, respectively; P = 0.0004123). At hypnotic doses, the effects of MOC-carboetomidate on arterial blood pressure and adrenocortical function were not significantly different from those of vehicle alone. CONCLUSIONS: MOC-carboetomidate is a GABA(A) receptor modulator with potent hypnotic activity that is more rapidly metabolized and cleared from the brain than carboetomidate, maintains hemodynamic stability similar to carboetomidate, and does not suppress adrenocortical function.

Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.

BACKGROUND: Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. METHODS: A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min. RESULTS: The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomidate > carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. CONCLUSIONS: Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative-hypnotic maintenance agents when hemodynamic stability is desirable.

Survey on aspirin application and ischemic stroke recurrence among elderly patients in Shanghai community hospitals / 上海第二医科大学学报

Objective To investigate the application status of aspirin for secondary prevention among elderly patients with ischemic stroke in some community hospitals in Shanghai,and explore the main causes for inappropriate use of aspirin and the effect of aspirin on the prevention of ischemic stroke recurrence. Methods The cross-sectional investigation was employed,and 223 patients from 10 community hospitals of Shanghai were divided into regularly-received aspirin group(n=98) and irregularly-received aspirin group(n=125).The application status of aspirin was investigated and the relationship between aspirin application and ischemic stroke recurrence was explored. Results Fifty-one cases in irregularly-received aspirin group(40.80%) stopped aspirin use or reduced the dose due to possible adverse effects,which accounted for 22.87% of the total population investigated,and 42 cases in irregularly-received aspirin group(33.60%)were never suggested to use aspirin or only used traditional Chinese medicine.The rate of ischemic stroke recurrence was 30.61%(30 cases) in regularly-received aspirin group,and 49.60%(62 cases) in irregularly-received aspirin group,which existed significant differences between these two group(P

Pharmacoeconomic analysis of three new chemotherapeutic regimens for non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate three new chemotherapeutic regimens for non-small cell lung cancer (NSCLC) by pharmacoeconomic analysis in guiding rational use of drugs.</p><p><b>METHODS</b>One hundred and one cases of NSCLC in clinic stage III or IV were treated by one of the three chemotherapeutic schemes-PC: paclitaxel (135mg/m²,d1)+DDP; TC: docetetaxel (75mg/m²,d1)+DDP; VC: vinorelbine (25mg/m²,d1 and d8)+DDP, DDP were given at 80mg/m² in 3 groups. Pharmacoeconomic cost-effectiveness analysis was used to compare the efficacy of the three regimens.</p><p><b>RESULTS</b>The response rate was 46.9%, 48.6% and 47.1% and median survival duration was 7.8, 7.5 and 7.6 months for PC, TC and VC regimen respectively, with 1-year survival rate of 37.5%, 37.1% and 38.2% respectively. There was remarkable difference in the response rate and median survival duration between PC and TC, but no statistical difference was observed between PC and VC. There was no statistical difference in 1-year survival rate among the three regimens. The average cost of one patient for one therapeutic cycle was RMB 15840.5, 15831.1 and 9401.8 Yuan respectively. Escalation of 1% of response rate costed RMB 337.75, 325.74 and 199.61 Yuan respectively. Prolongation of 1 month of median survival duration costed RMB 2030.83, 2110.97 and 1237.08 Yuan respectively. Escalation of 1% of one year survival rate costed RMB 422.41 , 426.71 and 246.12 Yuan respectively.</p><p><b>CONCLUSIONS</b>Among these three new chemotherapeutic regimens for the advanced patients with NSCLC, the expenditure of VC is much cheaper than PC and TC. The cost effectiveness of VC is the lowest among the three regimens.</p>