Therapeutic Effects of Traditional Chinese Medicine for Patients With Coronary Heart Disease After Treatment of Revascularization: A Prospective Cohort Study in the Northern of China.

Aim: To investigate the compliance and the outcome of Traditional Chinese Medicine (TCM) in patients with coronary heart disease (CHD) after treatment of revascularization. Methods: In this prospective cohort study, the non-exposure group (NEG), low-exposure group (LEG), and high-exposure group (HEG) were divided after 2 years follow-up. The primary outcome was a composite of death from cardiovascular causes, non-lethal myocardial infarction, heart transplantation, or stroke. Time-to-event data were evaluated by using the Cox regression analysis with hazard ratios (HRs) and 95% CIs. Then, the two-sided p-values were calculated by using the Cox models. In order to indicate the therapeutic effects of TCM on the CHD after revascularization, the survival analysis and the nested case-control study were conducted separately. Results: There were 1,003 patients with CHD enrolled, 356 patients (35.49%) did not choose the TCM, 379 patients (37.79%) used the TCM seldom, and only 268 patients (26.72%) used TCM regularly. A total of 653 patients with revascularization participated in the prospective cohort study. Over the duration of the trial, the primary endpoints occurred in 12 (4.35%), 11 (4.80%), and 2 (1.35%) patients in the NEG, LEG, and HEG, while the secondary endpoints occurred in 84 (30.43%), 57 (24.89%), and 15 (10.14%) patients in the NEG, LEG, and HEG, respectively. The occurrence time of secondary endpoint events in HEG was significantly postponed (p < 0.001) compared with the other cohorts. The Cox regression analysis indicated that the HRs in the primary endpoints, the secondary endpoint events, the major adverse cardiac and cerebrovascular events (MACCE), and the composite endpoint events for HEG were all around 0.3 (p < 0.05) and HRs for LEG were all around 0.8. The results of the nested case-control study showed that the TCM exposure was significantly different between the cases and controls in the secondary endpoints (p < 0.05), while no significant difference in the primary endpoints (p > 0.05), but the percentage of HEG in the cases was extremely lower than the controls. Conclusion: The HEG-TCM may improve the outcomes of the patients with CHD after treatment of revascularization. Registration: http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-17012995.

Hyperthermia ablation combined with transarterial chemoembolization versus monotherapy for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID-19 crisis. However, the evidence for decision-making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. MATERIALS AND METHODS: Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta-analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Thirty-six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5-year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p < 0.05) without increasing toxicity (p ≥ 0.05). Compared with TACE alone, HATACE was associated with superior 5-year OS rate (OR:3.54; 95%CI:1.96,6.37; p < 0.05) and significantly reduced the incidences of severe liver damage (OR:0.32; 95%CI:0.11,0.96; p < 0.05) and ascites (OR:0.42; 95%CI:0.20,0.88; p < 0.05). Subgroup analysis results of small (≤3 cm) HCC revealed that there were no significant differences between the HATACE group and HA monotherapy group in regard to the OS rates (p ≥ 0.05). CONCLUSIONS: Compared with TACE alone, HATACE was more effective and safe for HCC. Compared with HA alone, HATACE was more effective for non-small-sized (>3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC.

Dissecting Machine-Learning Prediction of Molecular Activity: Is an Applicability Domain Needed for Quantitative Structure-Activity Relationship Models Based on Deep Neural Networks?

Deep neural networks (DNNs) are the major drivers of recent progress in artificial intelligence. They have emerged as the machine-learning method of choice in solving image and speech recognition problems, and their potential has raised the expectation of similar breakthroughs in other fields of study. In this work, we compared three machine-learning methods-DNN, random forest (a popular conventional method), and variable nearest neighbor (arguably the simplest method)-in their ability to predict the molecular activities of 21 in vivo and in vitro data sets. Surprisingly, the overall performance of the three methods was similar. For molecules with structurally close near neighbors in the training sets, all methods gave reliable predictions, whereas for molecules increasingly dissimilar to the training molecules, all three methods gave progressively poorer predictions. For molecules sharing little to no structural similarity with the training molecules, all three methods gave a nearly constant value-approximately the average activity of all training molecules-as their predictions. The results confirm conclusions deduced from analyzing molecular applicability domains for accurate predictions, i.e., the most important determinant of the accuracy of predicting a molecule is its similarity to the training samples. This highlights the fact that even in the age of deep learning, developing a truly high-quality model relies less on the choice of machine-learning approach and more on the availability of experimental efforts to generate sufficient training data of structurally diverse compounds. The results also indicate that the distance to training molecules offers a natural and intuitive basis for defining applicability domains to flag reliable and unreliable quantitative structure-activity relationship predictions.

[Complex network analysis of law on Chinese herbal drugs intervention on radiation induced lung injury].

To mainly analyze the prescription rules of Chinese herbal drugs for radiation induced lung injury, optimize the prescriptions, and provide a reference for the clinical treatment of radiation induced lung injury. The major Chinese databases CNKI, CBM and Wanfang data were searched to obtain the literature on Chinese herbal drugs for radiation induced lung injury. BICOMS 2 software was used to extract and collect all Chinese herbal drugs information and generate the co-occurrence matrix; NetDraw and Gcluto software were then used to make network map and visualization matrix for analysis. A total of 552 articles (19 types and 304 Chinese herbal drugs) were included. Ophiopogon japonicus had the highest frequency (229 times), followed by Astragalus membranaceus(181 times), Glycyrrhiza uralensis (166 times), and Scutellaria baicalensis (150 times). After the classification of efficacy, deficiency-supplementing medicinal (69 kinds of Chinese herbs), heat-clearing medicine (51 kinds of Chinese herbs) and phlegm cough medicine (42 kinds of Chinese herbs) accounted for 53.29% of all the Chinese herbs, acting in the main position. After the prescription analysis for the top 25 herbal prescriptions, six main structures of common prescriptions were found for the treatment of radiation induced lung injury. There are many kinds of Chinese herbal drugs for the treatment of radiation induced lung injury in clinical application. In the future, researchers can mainly focus on Ophiopogon japonicus etc. as the main drugs, combine with other high-frequency Chinese herbal drugs found in this study, or directly refer to the main structures of commonly used prescriptions found in this analysis.

Effect of respiratory guidance on internal/external respiratory motion correlation for synchrotron-based pulsed heavy-ion radiotherapy.

Having implemented an audio-visual biofeedback (BFB) method for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery with tracking of external abdominal wall motion, this study evaluated the feasibility of the respiratory guidance method on thoracic and abdominal cancer patients, and the internal/external respiratory motion consistency under respiratory guidance maneuvers due to its interactive intervention in free breathing (FB). A total of 42 breathing traces from seven lung and breast cancer patients and corresponding fluoroscopy movies under FB, standard breath hold (stBH) and representative breath hold (reBH) guidance maneuvers were analyzed. Diaphragm motions were measured manually on a frame-by-frame basis. Mean absolute deviation (MAD) values of the measured external motion curves were calculated for the FB and guidance maneuvers, and the internal/external motion consistencies were compared with a linear fit. Compared with FB, the MAD values were reduced significantly with respiratory guidance maneuvers. The mean internal/external correlations of the first treatment fraction were determined to be 0.96 ± 0.03, 0.97 ± 0.02, and 0.97 ± 0.03 for the FB, stBH and reBH guidance maneuvers, respectively, and were 0.95 ± 0.03, 0.97 ± 0.03, and 0.98 ± 0.02 for the second treatment fraction. No phase shift between the two breathing signals was observed, and good reproducibility of consistency of breathing guidance between the two fractions was achieved. These results demonstrated that treatment precision could be improved for cancer patients with audio-visual BFB, and a strong correlation between diaphragm motion and abdominal wall motion was obtained. The use of audio-visual BFB improved the regularity of both internal and external motions, allowing confident use of the audio-visual BFB method by tracking of the external abdominal wall motion to synchrotron-based heavy-ion radiotherapy.

[Effect of electroacupuncture on proprioception in cynomolgus monkeys after unilateral anterior cruciate ligament injury].

OBJECTIVE: To study the effect of electroacupuncture on proprioception in cynomolgus monkeys after unilateral anterior cruciate ligament (ACL) injury. METHODS: Twenty-seven cynomolgus monkeys were randomized equally into 3 groups, namely unilateral ACL injury with electroacupuncture group, unilateral ACL injury model group and blank control group. One week after modeling, the monkeys in electroacupuncture group were treated daily for 12 weeks with electroacupuncture at the acupoints Wei Yang, Yin Gu, Xi Yangguan and Qu Quan. At 4, 8, and 12 weeks during the treatment, the changes in the somatosensory evoked potentials (SEPs) and motor nerve conduction velocity (MCV) of the nerves of the ACL were examined with neural electrophysiological method; the changes in the morphology and the total and variable number of the proprioceptors in the ACL were observed with gold chloride staining. RESULTS; In the mokeys in the model group, the incubation period of the SEPs and MCV on the injured side of the knee were significantly extended and the amplitudes were decreased with the passage of time (P<0.05). Intervention with electroacupuncture significantly reduced the incubation period and increased the amplitudes of the SEPs and MCV (P<0.05). The total number of the proprioceptors in the ACL was significantly decreased and the variable number of the proprioceptors in ACL was increased with time in the monkeys in the model group (P<0.05); electroacupuncture intervention obviously slowed the reduction rate of total number of the proprioceptors (P<0.05) but without affecting the variable number of the proprioceptors (P>0.05). CoONCLUSION: ACL injury causes attenuation of the proprioception on the injury side, and electroacupuncture intervention can produce a positive effect on the proprioception in cynomolgus monkeys.

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

RATIONALE: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes. OBJECTIVE: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes. METHODS AND RESULTS: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption. CONCLUSIONS: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.

Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1.

Initial high throughput screening efforts identified highly potent and selective kappa opioid receptor antagonist 3 (κ IC(50)=77 nM; µ:κ and δ:κ IC(50) ratios>400) which lacked CNS exposure in vivo. Modification of this scaffold resulted in development of a series of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides showing potent and selectivity κ antagonism as well as good brain exposure. Analog 6c (κ IC(50)=20 nM; µ:κ=36, δ:κ=415) was also shown to reverse κ-agonist induced rat diuresis in vivo.