Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.
Antineoplastic Agents/pharmacology* ; Bayes Theorem ; Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/drug therapy*

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

Arsenic is a potent toxic heavy metal found in the environment that can causes health problems, including liver disease in humans and animals. Chronic exposure to arsenic remains an environmental health problem worldwide, affecting hundreds of millions of people. Although the oxidative stress and apoptosis induced by arsenic have been confirmed, the underlying mechanism of apoptosis has not been fully elucidated. The purpose of this study is to investigate whether sodium arsenite (SA)induced liver toxicity is related to the regulation of DNA replication and repair pathways. The results of MTT and microscopy showed that SA has an inhibitory effect on the proliferation of human hepatocytes (L02), and this effect is time and concentration dependent. Flow cytometry detected the effects of different concentrations of SA on L02 cells. Compared with the control group, high concentrations of SA significantly affected the L02 cell cycle. In addition, RNA sequencing results showed that the differentially expressed genes in cells after SA treatment were concentrated in the DNA replication process and repair pathways. The effect of SA treatment on the expression of human RECQ DNA helicase and repair genes was further confirmed by Western blot and real-time quantitative PCR. In vitro study showed that SA treatment inhibited cell proliferation, and induced apoptosis as well as DNA damage and cell cycle arrest of human liver cell L02. Collectively, these results indicate that arsenic poisoning is related to the regulation of DNA replication and repair pathways, which provides insight for understanding the molecular mechanism of arsenic poisoning.

Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the life of the elderly and there is no effective therapy to treat or delay the onset of this disease. Due to the multifactorial etiology of this disease, the multi-target-directed ligand (MTDL) approach is an innovative and promising method in search for new drugs against AD. In order to find potential multi-target anti-AD drugs through reposition of current drugs, the database of global drugs on market were mined by an anti-AD multi-target prediction platform established in our laboratory. As a result, inositol nicotinate, cyproheptadine, curcumin, rosiglitazone, demecarium, oxybenzone, agomelatine, codeine, imipramine, dyclonine, melatonin, perospirone, and bufexamac were predicted to act on at least one anti-AD drug target yet act against AD through various mechanisms. The compound-target network was built using the Cytoscape. The prediction was validated by molecular docking between agomelatine and its multiple targets, including ADORA2A, ACHE, BACE1, PTGS2, MAOB, SIGMAR1 and ESR1. Agomelatine was shown to be able to act on all the targets above. In conclusion, the potential drugs for anti-AD therapy in the database for global drugs on market was partially uncovered using machine learning, network pharmacology, and molecular docking methods. This study provides important information for drug reposition in anti-AD therapy.

Cellular energy metabolism disorder caused by dysfunction of nutrient utilization and mitochondrial damage contributes to a variety of diseases, including neurodegenerative diseases, cancer, metabolic diseases, and cardiovascular diseases. Understanding the effects of energy metabolism on diseases will help to improve our knowledge about disease etiology and may serve to develop strategies to delay disease progress. There are many compounds developed for targeting energy metabolism disorders, such as small molecules targeting the 18 kDa transporter (TSPO) for treatment of Alzheimer's disease, glucagon-like peptide-1 analogues for treatment of Parkinson's disease, inhibitors of glucose transporter 1 (GLUT1) and lactate dehydrogenase A for treatment of tumors, the fibroblast growth factors based treatment for type 2 diabetes (T2D), selective ligands of peroxisome proliferator-activated receptor (PPAR)-β/δ for treatment of cardiovascular diseases. We review here the abnormal energy metabolism of common energy metabolism disorder-related diseases, summarize the potential targets that may be used for new drug discovery, and the strategies for alleviating the disease process by improving energy metabolism.

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (P<0.05), but there was no significant change in control group; the concentrations of CK-MB, cTNI, MYO and NT-pro-BNP in treatment group were significantly lower than those in control group(P<0.05), and the electrocardiogram QTc interval in the treatment group was significantly lower than that in the control group (P<0.05); echocardiography indexes E/A ratio and left ventricular ejective fraction (LVEF) value in the treatment group were significantly higher than those in control group (P<0.05). There were no significant changes in left ventricular end-systolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) between the treatment and the control group. After 3 cycles and 6 cycles of chemotherapy, the blood NE,E and AngⅡ concentrations in the treatment group were significantly lower than those in the control group (P<0.05). There were positive linear correlation in concentration changes of blood NE, E and AngⅡ as well as the concentration changes of CK-MB, cTNI, MYO and NT-pro-BNP between 3 cycles and 6 cycles after chemotherapy. After 6 cycles of chemotherapy, the incidence of cardiovascular events in the treatment group was significantly lower than that in the 3 cycles of chemotherapy, while the incidence in control group was increased. Conclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.

Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10(9)/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion: BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.
Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Pneumonia/etiology* ; Prospective Studies

OBJECTIVETo establish the association between the geometric anatomical characteristics of the patients and the corresponding three-dimensional (3D) dose distribution of radiotherapy plan via feed-forward back-propagation neural network for clinical prediction of the plan dosimetric features.

METHODSA total of 25 fixed 13-field clinical prostate cancer intensity-modulated radiation therapy (IMRT)/stereotactic body radiation therapy (SBRT) plans were collected with a prescribed dose of 50 Gy. With the distance from each voxel to the planned target volume (PTV) boundary, the distance from each voxel to each organ-at-risk (OAR), and the volume of PTV as the geometric anatomical characteristics of the patients, the voxel deposition dose was used as the plan dosimetric feature. A neural network was used to construct the correlation model between the selected input features and output dose distribution, and the model was trained with 20 randomly selected cases and verified in 5 cases.

RESULTSThe constructed model showed a small model training error, small dose differences among the verification samples, and produced accurate prediction results. In the model training, the point-to-point mean dose difference (hereinafter dose difference) of the 3D dose distribution was no greater than 0.0919∓3.6726 Gy, and the average of the relative volume values corresponding to the fixed dose sequence in the DVH (hereinafter DVH difference) did not exceed 1.7%. The dose differences among the 5 samples for validation was 0.1634∓10.5246 Gy with percent dose differences within 2.5% and DVH differences within 3%. The 3D dose distribution showed that the dose difference was small with reasonable predicted dose distribution. This model showed better performances for dose distribution prediction for bladder and rectum than for the femoral heads.

CONCLUSIONWe established the relationships between the geometric anatomical characteristics of the patients and the corresponding planning 3D dose distribution via feed-forward back-propagation neural network in patients receiving IMRT/SBRT for the same tumor site. The proposed model provides individualized quality standards for automatic plan quality control.