Qiliqiangxin capsule improves cardiac remodeling in rats with DOCA-salt-induced diastolic dysfunction.

OBJECTIVE: The aim of this study was to investigate the protective effect and mechanism of action (MOA) of Qiliqiangxin capsule (QL) in the deoxycorticosterone acetate (DOCA) salt-induced rat heart failure with preserved ejection fraction (HFpEF) model. MATERIALS AND METHODS: Nono-nephrectomy sixty Sprague Dawley (SD) rats received DOCA salt injection and 1% saline in drinking water for 4 weeks and were randomly divided into four groups on average: Model group (n=15), Sac/Val group (Sacubitril Valsartan 0.02 g/kg, n=15), QL-L group (Qiliqiangxin 0.25 g/kg, n=15) and QL-H group (Qiliqiangxin 1 g/kg, n=15). Another Normal group was set (n=15). Blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac index, echocardiography, and hemodynamics were measured to evaluate heart function. Masson and Wheat germ agglutinin (WGA) staining was performed to observe the fibrosis deposition and the cross-sectional area (CSA) of cardiomyocytes. The concentration levels of the serum cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and IL-10 inflammatory factors, were detected by ELISA; matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), transforming growth factor-ß1 (TGF-ß1), nuclear factor-κB (NF-κB), Smad homologue 2 (Smad2) and Smad homologue 3 (Smad3) expression were detected by Western-blot. RESULTS: Compared with the Model group, QL treatment significantly ameliorated the heart function in DOCA salt-induced rat HFpEF model, showing a decrease in cardiac index, an increase of the EF and E/A ratio, a reduction in the left ventricular anterior/posterior wall (LVAW/LVPW), in the time contraction of isovolumic diastolic time (IVRT), -dP/dt Max, and Tau, and the decrease of serum NT-ProBNP. Masson and WGA staining indicated that QL inhibited the fibrosis deposition and the myocardial hypertrophy compared with the Model group, which was consistent in reducing the protein expression levels of cardiac remodeling such as TGF-ß1, MMP2, MMP9, Smad2, and Smad3. Moreover, QL treatment inhibited the expression of NF-κB in the heart tissues and decreased the serum concentration of pro-inflammatory cytokines TNF-α and IL-2, instead, increasing the IL-10 concentration. CONCLUSIONS: QL improved the cardiac function and inhibited the myocardial fibrosis in DOCA salt-induced rat HFpEF by improving diastolic dysfunction, preventing left ventricular hypertrophy, and ameliorating the inflammatory responses model in DOCA salt-induced rat HFpEF model.

[Analysis of the feasibility and prognostic value of circulating tumor DNA in detecting gene mutations in small cell lung cancer].

Objective: To investigate the feasibility of circulating tumor DNA (ctDNA) in detecting small cell lung cancer (SCLC) gene mutations and its prognostic value in chemotherapy and/or radiotherapy for SCLC patients. Methods: A total of 77 SCLC patients who were admitted to the Department of Thoracic Medical Oncology and the Department of Thoracic Radiation Oncology of Zhejiang Cancer Hospital from July 2016 to November 2019 were included. There were 66 males and 11 females, with a median age of 60 years. Among them, 42 cases were in limited stage (LS) and 35 cases were in extensive stage (ES). Next-generation sequencing (NGS) of patients' plasma ctDNA was performed before treatment. The differences of mutated genes and signaling pathways between LS and ES patients were analyzed and compared. Blood-based tumor mutation burden (bTMB) was calculated according to detected somatic cell mutations. Patients were divided into the high bTMB and the low bTMB groups according to the optimal threshold calculated by R software. Log-rank tests were used to compare progression-free survival (PFS) between the high bTMB and the low bTMB groups. Results: Among the 77 patients, 76 patients had gene mutations detected in their plasma, and the positive rate of ctDNA test was 98%. Among the 76 patients, the genes with the highest mutation frequency were TP53 (89%), RB1 (70%), LRP1B (34%), CREBBP (21%), MLL3 (21%), MLL2 (16%), NOTCH1 (13%), ROS1 (13%), BRCA2 (12%), and PTPRD (12%). The most common mutated genes in LS patients were TP53 (90%), RB1 (68%), LRP1B (24%), MLL2 (22%), and BRCA2 (17%); the most common mutated genes in ES patients were TP53 (89%), RB1 (71%), LRP1B (46%), CREBBP (31%), and MLL3 (29%). The mutation rates of NOTCH1 and CREBBP genes were significantly higher in ES patients (31.4% and 22.9%) than those in LS patients (11.9% and 4.8%) (both P<0.05). Signaling pathway analysis showed that there were more NOTCH pathway gene variations in ES patients. Among LS patients, patients in the high bTMB group (≥ 6.96 mutations/Mb) had a longer PFS than that in the low bTMB group (<6.96 mutations/Mb) (P=0.033); but no such difference was noted in ES patients. Conclusion: Plasma ctDNA sequencing detected SCLC gene mutation profiles similar to those reported in previous literature, thus ctDNA could be used as a tool to study SCLC genomics; the mutation spectra of ES-SCLC and LS-SCLC were different. bTMB has potential prognostic value in LS-SCLCs treated with chemoradiotherapy.

Interdisciplinary communication in the intensive care unit at the University Hospital of the West Indies.

OBJECTIVE: To assess the perceptions of physicians and nurses working full-time in the Intensive Care Unit (ICU) at the University Hospital of the West Indies (UHWI) regarding interdisciplinary communication. METHOD: A cross-sectional survey of all medical personnel working full-time in the ICU was conducted in January 2008 using a self-administered, validated questionnaire. Data on perceived communication, teamwork and leadership, comprehension of patient care goals, perceived effectiveness and satisfaction were collected and analysed using the SPSS Version 14. Internal reliability was tested using Cronbach's alpha score and differences and correlations were assessed using Pearson's Chi-square and correlation analysis. RESULTS: Ninety-five per cent (105/111) of questionnaires were completed. More doctors than nurses experienced open communication with other staff members (73% vs 32%; p < 0.01), with less openness occurring with increasing seniority. More doctors (53%) than nurses (32%) reported receiving inaccurate information from doctors (p < 0.05), with 67% and 51% respectively receiving incorrect information from nurses (p < 0.05). Communication across shifts was felt to be better amongst doctors than nurses (73% vs 63%). Only 50% of doctors compared to 88% of nurses felt they received relevant information quickly (p < 0.05). More nurses than doctors (86% vs 63%; p < 0.01) felt that they had a good understanding of patient care goals. Negative perceptions of the leadership characteristics of consultants (62% amongst doctors and 74% of nurses) and sisters (79% and 73%, respectively) were high. CONCLUSIONS: Communication within the ICU, UHWI, is unsatisfactory with an overall poor perception of senior leadership. Improvement in staff morale and leadership training may create a working environment where team members can communicate openly without fear of chastisement.

Thallium-201 SPECT predicts response to intensity-modulated radiation therapy for recurrent oral squamous cell carcinoma.

UNLABELLED: The aim of this study was designed to investigate the usefulness of thallium-201 single photon emission computed tomography (SPECT) in predicting response of intensity-modulated radiation therapy (IMRT) for recurrent oral squamous cell carcinoma (OSCC). PATIENTS, METHODS: Thirty-one patients with histologically proven recurrent OSCC were recruited. Before IMRT, all patients underwent SPECT at 15 min and 120 min after intravenous injection 111 MBq of thallous chloride ((201)Tl). Tumour uptake was measured with the semiquantitative early ratio (ER), delayed ratio (DR), and retention index (RI). The patients were classified into responder (complete response and partial response) and non-responder (stable disease and progressive disease) groups according to the tumour response evaluated by the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: As comparing DR and RI between the two groups, both parameters were significantly higher in the responder group. When a DR of 1.75 was used as a cutoff value for the responders, the receiver operating characteristic (ROC) analyses revealed sensitivity and specificity of 79% and 75%, respectively. At a cutoff value for the responders of a RI of 78.5%, the ROC analyses showed sensitivity and specificity of 95% and 83%, respectively. CONCLUSION: Our results suggest that (201)Tl-SPECT, as measured by the DR or RI has clinical potential in predicting response of IMRT for patients with recurrent OSCC. The ROC curve analyses further suggest that RI may be superior to DR in distinguishing responders from non-responders.

Comparision of interleukin-6 and malondialdehyde levels in diabetic patients in Taiwan.

The purpose of this study was to compare the levels of interleukin-6 (IL-6) and malondialdehyde (MDA) in healthy controls and diabetic patients without coronary heart disease (CHD). Fasting serum IL-6 and MDA were determined in 30 healthy controls and 52 (20 Type 1 and 32 Type 2) diabetic patients without clinical evidence of CHD. MDA was calculated as oxidative stress. The IL-6 concentration was used to evaluate the cytokine function. Results showed that the serum IL-6 and MDA concentrations are significantly higher in Type 2 diabetic patients (p<0.05). In conclusion, we demonstrated that Type 2 diabetic patients are more influenced by oxidative stress than Type 1 diabetic patients and healthy controls, because of the action of cytokine.

Different risks of symptomatic brain necrosis in NPC patients treated with different altered fractionated radiotherapy techniques.

PURPOSE: To report our observation of excessive temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients treated with 160 cGy b.i.d. radiotherapy technique. During the same period, patients treated with 120 cGy b.i.d. have not shown a similar tendency. Our experience may be useful for designing unconventional radiotherapy regimens for NPC patients. METHODS AND MATERIALS: During the period from October 1991 to January 1998, 81 M0, previously untreated NPC patients completed altered fractionated radiotherapy. Seventy patients were treated with the hyperfractionated technique, and 11 were treated using the accelerated-hyperfractionated scheme. Hyperfractionated radiotherapy was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. A minimum tumor dose of 8000 cGy was the standard dose over an 8-week period. With the accelerated-hyperfractionated scheme, 160 cGy was given twice daily, also with an interval of 6 h. The minimum tumor dose ranged between 6840 and 7640 cGy, with 7 of the 11 patients receiving 7000 cGy. The arrangement of portals was the same for both regimens. The follow-up period for patients alive was from 32 to 102 months with a median of 61 months for the hyperfractionated patients. For the accelerated-hyperfractionated group, it ranged from 67 to 82 months with a median of 72 months. No patient was lost to follow-up. RESULTS: At the time of analysis, 49 of the 70 patients in the hyperfractionated group were alive. In the accelerated group, 8 of the 11 patients were alive. The estimated radiation dose to the temporal lobe for the hyperfractionated group was 6000-7440 cGy with a median of 7080 cGy. For the accelerated-hyperfractionated group, the dose range was 4480-6700 cGy with a median of 6400 cGy. Of the 70 patients treated with hyperfractionated radiotherapy, none developed symptomatic brain necrosis, despite the higher total dose to the temporal lobe in general. In contrast, 3 of the 11 (27%) patients irradiated using the accelerated-hyperfractionated regimen suffered from temporal lobe necrosis at 16, 19, and 40 months after completion of radiotherapy. CONCLUSION: An excessive incidence of temporal lobe necrosis was noted when an accelerated-hyperfractionated regimen with 160 cGy b.i.d. was used in NPC patients with a median brain dose of 6400 cGy. There has been no such event in patients treated using a hyperfractionated regimen with 120 cGy and a median brain dose of 7000 cGy. The real causes of this discrepancy are not known. However, a high sensitivity of the human brain to a change in fraction size may play a role.

Direct interaction of two homeoproteins, homothorax and extradenticle, is essential for EXD nuclear localization and function.

The Drosophila Homothorax (HTH) and Extradenticle (EXD) are two homeoproteins required in a number of developmental processes. EXD can function as a cofactor to Hox proteins. Its nuclear localization is dependent on HTH. In this study we present evidence of in vivo physical interaction between HTH and EXD, mediated primarily through an evolutionarily conserved MH domain in HTH. This interaction is essential for the mutual stabilization of both proteins, for EXD nuclear localization, and for the cooperative DNA binding of the EXD-HTH heterodimer. Some in vivo functions require both EXD and HTH in the nucleus, suggesting that the EXD-HTH complex may function as a transcriptional regulator.

Harziphilone and fleephilone, two new HIV REV/RRE binding inhibitors produced by Trichoderma harzianum.

During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol-methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0 microM and 7.6 microM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200 micrograms/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38 microM against the murine tumor cell line M-109.

Ascosteroside, a new antifungal agent from Ascotricha amphitricha. I. Taxonomy, fermentation and biological activities.

Ascosteroside, a novel antifungal compound, was isolated from the culture broth of Ascotricha amphitricha. This compound is an alpha-linked glycoside of a lanostane type triterpenoid. It is active against yeasts such as Candida albicans and Saccharomyces cerevisiae and against filamentous fungi but shows no activity against bacteria. It is not toxic to mammalian cells at concentrations up to 150 microM. In a mouse model, the compound afforded protection comparable to that of ketoconazole.

Maximal breath-holding time and immediate tissue CO2 storage capacity during head-out immersion in humans.

This study tested three possible mechanisms that could explain the prolonged breath-holds (BH) previously observed in humans during submersion in 35 degrees C (thermoneutral) water, including a reduced metabolism, a decreased CO2 sensitivity, and an increased CO2 storage capacity. During immersed BH (n = 13), maximal BH time was prolonged by 20.3% (P < 0.05), the rate of rise of end tidal partial pressure of carbon dioxide (PETCO2) was slower (P < 0.05) by 31% (compatible with increased CO2 storage capacity), but the breaking-point PETCO2 (CO2 sensitivity) and the rate of decrease of end tidal partial pressure of oxygen (metabolism) were unchanged. During air breathing (n = 5), immersion resulted in a significant decrease in tidal volume (11%), but did not affect O2 uptake, CO2 elimination (VCO2), or respiratory exchange ratio (R). During a 4-min CO2-rebreathing (n = 9), the slope of the hypercapnic ventilatory response curve (CO2 sensitivity index) was unchanged by immersion, but the significantly decreased VCO2, R, and rate of rise in PETCO2 during immersed rebreathing indicated an increase in the acute CO2 storage capacity (SC). The estimated SC (n = 9), based on an assumed cellular respiratory quotient of 0.8, were 0.52 (SEM 0.03) ml.kg-1.mmHg-1 for control and 0.66 (SEM 0.04) ml.kg-1.mmHg-1 for immersion. A proposed mechanism for the increased SC during immersed BH and during immersed rebreathing is that immersion accelerated CO2 redistribution in the body by increasing perfusion to some low-perfused, low-metabolism, and high-capacity tissues, such as resting skeletal muscle. The increased SC during immersion, however, did not correlate with the prolonged BH duration (n = 9, P > 0.05). The mechanism of the latter remains unclear.

CO2 chemosensitivity during immersion in humans.

Hypercapnic ventilatory response was compared in 9 seated subjects during head-out immersion in 35 degrees C (thermoneutral) water and during non-immersion in 28 degrees C (thermoneutral) room air. Using Read's CO2-rebreathing technique, minute ventilation (VE) and end-tidal (ET) PCO2 were sampled continuously for 4-5 min with a spirometer and a mass spectrometer, while the subject rebreathed a 6 L gas mixture initially containing 7% CO2 and 93% O2 in a bag-in-box system. The slope of the hypercapnic ventilatory response curve, expressed as delta VE/delta PETCO2, ranged from 0.76 to 2.49 L/min/mmHg. Immersion affected neither the slope nor the position of the hypercapnic ventilatory response curve. The rate of rise of PETCO2 during immersed CO2-rebreathing was significantly reduced (4.47 +/- 0.19 [SE] mmHg/min), as compared to the control value (5.67 +/- 0.24). It was concluded that the CO2 chemosensitivity during immersion in humans did not change and that the capacity to store CO2 in tissue might have been increased.

Hyperbaric oxygen therapy in clinical application. A report of a 12-year experience.

Hyperbaric oxygen (HBO) has become a useful treatment in clinical diseases. All the treatment profiles (Death/Time) were performed under the safe limit of unit pulmonary toxicity dose (UPTD). Between June 1976 and December 1987, we had treated 1288 cases with HBO. The effective rates (cure or improvement) were 97.5% for decompression sickness, 96.3% for chronic osteomylitis, 90% for chronic skin ulcer, 89.4% for crush injury, 81.3% for gas intoxication, 76.1% for burn injury, 73.3% for cerebrovascular accident, 57.1% for gas gangrene, 50% for retinal artery insufficiency, and 45.5% for head or spinal cord injury. Only 3 patients suffered from oxygen toxicity and relieved immediately. To the serious decompression sickness, the comparative study between the conventional treatment table and our modified table revealed increased cure rate(25.8% versus 50.0%, P less than 0.05), and decreased recurrence rate (16.1% versus 4.1%, P less than 0.05). In burn patients with 35-70% area involved and 15-45 years of age, the comparative analysis showed a reduced mortality rate of 6.8% for the HBO treated group as opposed to 14.8% for the non-HBO treated group, P less than 0.05.

[Retention index of essential oil in temperature-programmed capillary column gas chromatography].

Kovats retention indexes of more than 200 kinds of natural and synthetic compounds of alcohol, aldehyde, acetal, ketone, ether, alkene, nitrile, carboxylic acid, ester, etc. were determined on polar liquid phase (DB-WAX) and nonpolar liquid phase (DB-1) by linear temperature-program capillary column gas chromatography. Some rules of part of the homologous series of compounds were summed up from the retention indexes: the rules of RI vs carbon, RI vs boiling point and RI on two columns. In order to keep the retention indexes practical, effects of initial temperature (T0), program rate (r) and average linear carrier gas velocity (u), etc. on the retention indexes were investigated. The conclusion is that the retention indexes are highly reproducible so long as the program parameters change in a certain range. Two kinds of essences, Meigui and Linglan, were identified successfully on IBM-PC/XT microcomputer by the Data Base Management System of essential oil and essence by capillary column gas chromatography and the results are satisfactory.

Resolution of stereoisomers of dipeptides by gas chromatography on Chirasil-Val.

Several dipeptides have been separated into stereoisomers (enantiomers, diastereomers, sequential isomers) by gas chromatography on Chirasil-Val. Sufficiently volatile N-trifluoroacetyl dipeptide methyl esters were formed at ambient temperature, thus avoiding racemization (or epimerization, respectively, and cleavage of the peptide bond. This method is suitable for ascertaining the stereoisomeric composition of dipeptides in biological samples.