Meta-path guided graph attention network for explainable herb recommendation.

Traditional Chinese Medicine (TCM) has been widely adopted in clinical practice by Eastern Asia people for thousands of years. Nowadays, TCM still plays a critical role in Chinese society and receives increasing attention worldwide. The existing herb recommenders learn the complex relations between symptoms and herbs by mining the TCM prescriptions. Given a set of symptoms, they will provide a set of herbs and explanations from the TCM theory. However, the foundation of TCM is Yinyangism (i.e. the combination of Five Phases theory with Yin-yang theory), which is very different from modern medicine philosophy. Only recommending herbs from the TCM theory aspect largely prevents TCM from modern medical treatment. As TCM and modern medicine share a common view at the molecular level, it is necessary to integrate the ancient practice of TCM and standards of modern medicine. In this paper, we explore the underlying action mechanisms of herbs from both TCM and modern medicine, and propose a Meta-path guided Graph Attention Network (MGAT) to provide the explainable herb recommendations. Technically, to translate TCM from an experience-based medicine to an evidence-based medicine system, we incorporate the pharmacology knowledge of modern Chinese medicine with the TCM knowledge. We design a meta-path guided information propagation scheme based on the extended knowledge graph, which combines information propagation and decision process. This scheme adopts meta-paths (predefined relation sequences) to guide neighbor selection in the propagation process. Furthermore, the attention mechanism is utilized in aggregation to help distinguish the salience of different paths connecting a symptom with a herb. In this way, our model can distill the long-range semantics along meta-paths and generate fine-grained explanations. We conduct extensive experiments on a public TCM dataset, demonstrating comparable performance to the state-of-the-art herb recommendation models and the strong explainability.

Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1α/VEGF Signaling Pathway.

Sjögren's syndrome (SS) which could lead to a disorder of our immune system is a chronic autoimmune disease characterized by invading exocrine glands such as salivary glands and lacrimal glands and other exocrine glands. Its common symptom is dry mouth and dry eyes, often accompanied by a large number of lymphocyte infiltrations and can involve other organs to cause complex clinical manifestations. In this study, we aimed at investigating the effect of QZF in SS, identifying the molecular mechanism in modulating autoimmune response, and determining the important roles of these factors' function as a modulator in the pathogenesis of SS. The NOD mice were utilized to establish the rats' model of Sjögren's syndrome. After 10 weeks' hydroxychloroquine and QZF in different dose interference, submandibular gland tissue was collected. The therapeutic effect of QZF on SS rats was identified, and the results suggest the comparable potential to hydroxychloroquine. In submandibular gland tissue, interleukin- (IL-) 17 was significantly lower in high-dose QZF than that in SS rats and the focal lymphocytes were highly attenuated. Moreover, we found that PI3K/Akt signals were activated and the downstream HIF-1α/VEGF signals were enhanced in SS rats whose protein expression could be inhibited by QZF treatment. In addition, QZF could modulate autophagy in submandibular gland tissue and then inhibit the inflammation response and therefore facilitate the tissue repair.

Protective effects and possible mechanisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies.

Drug-induced liver injury (DILI) has become a significant health care problem worldwide. Centella asiatica (L.) urban was traditionally used to prevent or treat various diseases, yet whether it works on hepatic injury remains unclear. In this study, multiple experimental models with different damage degrees and types of liver injury have been established to evaluate the hepatoprotective effects of an n-butanol extract of Centella asiatica (CA-BU). Our results revealed that CA-BU improved hepatocyte L02 cells survival from H2 O2 -induced oxidative damage in a concentration-dependent manner. We further verified the hepatoprotective effects of CA-BU in mice models of acetaminophen-induced acute liver injury (one of the most common DILIs clinically) and CCl4 -induced acute chemical liver injury, and a rat model of chronic alcoholic steatohepatitis. Furthermore, network pharmacology approaches were performed to explore the underlying mechanisms, and we predicted AKT1, EGFR, VEGFA, and STAT3 as the potential therapeutic targets. In follow-up studies, we will focus on targets verification and provide a deeper insight into the mechanisms of CA-BU against liver damage. Finally, we hope that these findings will provide new ideas and insights for the treatment of acute or chronic liver injury in the clinic.

[Resources industrialization channels and strategies of active polysaccharide from Lycii Fructus based on analysis of domestic and foreign intellectual properties].

Lycii Fructus is a traditional medicinal and edible herb, with the function of liver and kidney nourishing, blood and eyesight replenishing. As the most important active substance in the fruits of Lycium barbarum, Lycium barbarum polysaccharides (LBP) have been demonstrated to play multiple pharmacological activities, with broad prospects for development and utilization. Based on the comprehensive deep analysis of global LBP patent output, the current patent LBP features were explored from the perspective of development trend, technology field distribution, time dimension, technology life curve and patent applicant. The development trend of Chinese LBP industry was also revealed. At present, the research and development of LBP is in the "development period", with a good development track in which the main research institutions remain domestic ones. At the same time, problem still presents in the lack of industrialization, which means that the advantage of natural resources has not been transformed into industrial advantages of LBP. The format of potential product group and prospect of LBP were also analyzed to provide scientific information for the effective development,comprehensive utilization and collaborative innovation mechanism of Chinese Lycium barbarum resources and LBP.

[Effect of triptolide on the expression of RANTES in the renal tissue of diabetic nephropathy rats].

OBJECTIVE: To investigate the effect of triptolide (TPL) on the renal tissue of diabetic rats and its possible mechanisms. METHODS: SD rats were randomly divided into the normal control group (as the normal group), the diabetic model group (the model group), the low dose TPL treatment group (the low dose TPL group, TPL 0.2 mg/kg by gastrogavage), the high dose TPL treatment group (the high dose TPL group, TPL 0.4 mg/kg by gastrogavage). Equal volume of normal saline was given to rats in the normal group and the model group. Five rats were randomly selected from each group at week 4, 8, and 12 of the experiment to detect body weight, kidney weight, 24 h urinary albumin (24 h UAL), plasma glucose (FBG), total cholesterol (TC), total triglyeride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), and hemoglobin A1c (HbA1c). The mRNA and protein expression of regulated upon activation normal T-cell expressed and secreted (RANTES) in the renal tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The renal tissue was pathologically stained by HE, PAS, and Masson staining. The glomerular and renal tubular interstitial lesions were observed at each time point. The glomerular sclerosis index (GSI) was observed by PAS staining, and the renal interstitial filrosis index (RIFI) was calcutated. RESULTS: Compared with the same group at week 4, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 significantly decreased in two TPL groups (P <0.01). Compared with the same group at week 8, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 also significantly decreased in the two TPL groups (P <0. 05, P <0.01). Compared with the normal group, body weight and the kidney weight obviously decreased at week 4, 8, and 12 in the model group (P <0. 01); 24 h UAL, FBG, TG, TC, HbA1c, RANTES, GSI, and RIFI were obviously elevated (P <0.01). Compared with the model group, 24 h UAL, RANTES, GSI, and RIFI also decreased in the two TPL treatment groups (P <0.01). Compared with the low dose TPL group, they were attenuated in the high dose TPL group (P <0. 05, P <0. 01). CONCLUSION: TPL could not only inhibit the over-expression of RANTES, but also improve the glomerular sclerosis and renal interstitial fibrosis in the renal tissue of diabetic rats.

Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation.

Hyperbaric oxygen (HBO) is emerging as a therapy for brain ischemia, although its benefits are still debated. The present study aimed to investigate the effect of HBO on brain damage in a rat model of transient focal cerebral ischemia and its underlying mechanism of action. Male Wistar rats, which had suffered 1.5h of transient middle cerebral artery occlusion (tMCAO) and had a Longa's neuron score of 3, were given pure oxygen at 3.0 atm absolute, for 60 min after the third hour of reperfusion. After 24h of reperfusion, rat brains were removed and studied. 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin and eosin staining revealed that the infarct ratio in the HBO group increased remarkably when compared with the MCAO group. Up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation was detected in the HBO group because of reactive oxygen species (ROS) generation. Autophagy appeared to be obstructed in the HBO group. Administration of the ERK1/2 inhibitor U0126 decreased the infarct ratio and improved protein clearance by autophagy in the HBO group. Collectively, these results suggest that HBO enlarges the area of brain damage via reactive oxygen species-induced activation of ERK1/2, which interrupts autophagy flux.

A phase II study of preoperative chemotherapy with modified FOLFOX6 followed by surgery and postoperative chemoradiation in patients with localized gastric adenocarcinoma.

The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.

Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations.

AIM: Growing evidence indicates that the glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology and possibly the pathogenesis of major depressive disorders. This study is to evaluate the effect of gan mai da zao (GMDZ) decoction on glutamate and NMDA receptor in unpredictable chronic mild stress (UCMS) rats. MATERIALS AND METHODS: Sucrose preference test and open field test were used to estimate the depressive-like behaviors of UCMS rats. Glutamate levels and NMDA receptor subunits (NR1, NR2A and NR2B) in the frontal cortex and hippocampus were determined by HPLC-FLD and by western-blot respectively. RESULTS: 32 days UCMS induced depressive-like behaviors, increased glutamate concentration and decreased NMDA receptor subunits NR2A and NR2B in the frontal cortex and hippocampus of rats. However, NR1 expression remained constant in stressed rats compared with normal. The GMDZ decoction alleviated the depressive-like behavior, decreased glutamate level, and increased expression of NMDA receptor subunit NR2A and NR2B in the frontal cortex and hippocampus of stressed rats. CONCLUSIONS: These results suggest that GMDZ treatment reversed chronic unpredictable stress-induced depressive-like behaviors in UCMS rats, possibly via reducing glutamate levels and increasing the NMDA receptor subunits NR2A and NR2B in frontal cortex and hippocampus.