Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification.

BACKGROUND: Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and the existing treatments cannot meet the needs of today's patients. Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application. However, the specific mechanism by which it works is still unclear. Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) for the treatment of DKD will provide a new way of thinking for the research and development of new drugs. AIM: To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking, and then verify the initial findings by in vitro experiments. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredient targets of NRDP. Targets for DKD were obtained based on the Genecards, OMIM, and TTD databases. The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram, and Cytoscape 3.9.0 was used to build a "drug-component-target-disease" network. The String database was used to construct protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology analysis were performed based on the DAVID database. After selecting the targets and the active ingredients, Autodock software was used to perform molecular docking. In experimental validation using renal tubular epithelial cells (TCMK-1), we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability, with glucose solution used to mimic a hyperglycemic environment. Flow cytometry was used to detect the cell cycle progression and apoptosis. Western blot was used to detect the protein expression of STAT3, p-STAT3, BAX, BCL-2, Caspase9, and Caspase3. RESULTS: A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP. Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products (AGEs)-receptor for AGEs (RAGE) signaling as the core pathway. Molecular docking showed good binding between each active ingredient and its core targets. In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells, blocked cell cycle progression in the G0/G1 phase, and reduced apoptosis in a concentration-dependent manner. Based on the results of Western blot analysis, NRDP differentially downregulated p-STAT3, BAX, Caspase3, and Caspase9 protein levels (P < 0.01 or P < 0.05). In addition, BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced, while BCL-2 and STAT3 protein expression was upregulated (P < 0.01). CONCLUSION: NRDP may upregulate BCL-2 and STAT3 protein expression, and downregulate BAX, Caspase3, and Caspase9 protein expression, thus activating the AGE-RAGE signaling pathway, inhibiting the vitality of TCMK-1 cells, reducing their apoptosis. and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Prevalence, risk factors, and clinical characteristics of pulmonary embolism in patients with acute exacerbation of COPD in Plateau regions: a prospective cohort study.

BACKGROUND AND OBJECTIVE: To investigate pulmonary thromboembolism (PE) in acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) patients in plateau regions, we performed a prospective cohort study to evaluate the prevalence, risk factors and clinical characteristics of PE in the cohort of hospitalized patients at high altitude. METHODS: We did a prospective study with a total of 636 AE-COPD patients in plateau regions. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without PE. We also conducted logistic regression to explore the risk factors of PE. RESULTS: Of the 636 patients hospitalized with AE-COPD (age 67.0 ± 10.7 years, 445[70.0%] male), 188 patients developed PE (29.6% [95% CI: 26.0%, 33.1%]). Multivariable logistic regression showed that ethnic minorities, D-dimer > 1 mg/L, AST > 40 U/L, chest pain, cardiac insufficiency or respiratory failure, Padua score > 3, and DVT were associated with a higher probability of PE. CONCLUSIONS: The prevalence of PE is high and those with a higher Padua score, the occurrence of deep venous thrombosis, higher neutrophil count, chest pain, cardiac insufficiency or respiratory failure, higher levels of AST, and a higher level of D-dimer had a higher risk of PE. The analysis of AE-COPD may help to provide more accurate screening for PE and improve clinical outcomes of patients with AE-COPD in plateau regions.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking.

BACKGROUND: Diabetic nephropathy (DN) stands as the most prevalent chronic microvascular complication of diabetes mellitus. Approximately 50% of DN patients progress to end-stage renal disease, posing a substantial health burden. AIM: To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid (GA) treats DN, subsequently validating these predictions through experimental means. METHODS: The study initially identified GA targets using Pharm Mapper and the TCMSP database. Targets relevant to DN were obtained from the Genecards, OMIM, and TTD databases. The Venny database facilitated the acquisition of intersecting targets between GA and DN. The String database was used to construct a protein interaction network, while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. Molecular docking experiments were performed using Autodock software with selected proteins. Experimental validation was conducted using renal proximal tubular cells (HK-2) as the study subjects. A hyperglycemic environment was simulated using glucose solution, and the effect of GA on cell viability was assessed through the cell counting kit-8 method. Flow cytometry was employed to detect cell cycle and apoptosis, and protein immunoblot (western blot) was used to measure the expression of proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and insulin resistance pathway, including insulin receptor (INSR), PI3K, p-PI3K, AKT, p-AKT, and glycogen synthase kinase-3 (GSK3). RESULTS: A total of 186 intersecting targets between GA and DN were identified, which were associated with 144 KEGG-related enrichment pathways, 375 GO biological process entries, 45 GO cellular component entries, and 112 GO cellular function entries. Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase (MAPK)-1, SRC, PIK3R1, HSP90AA1, CASPASE9, HARS, KRAS, and MAPK14. In vitro experiments revealed that GA inhibited HK-2 cell viability, induced cell cycle arrest at the G2/M phase, and reduced apoptosis with increasing drug concentration. Western blot analysis showed that GA differentially up-regulated GSK3 protein expression, up-regulated AKT/p-AKT expression, down-regulated INSR, AKT, p-AKT, PI3K, and p-PI3K protein expression, and reduced p-PI3K/PI3K levels under high glucose conditions. CONCLUSION: GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway, thereby inhibiting HK-2 cell viability, reducing HK-2 cell apoptosis, and inducing cell cycle arrest at the G0/G1 phase.

Identification and immunological characterization of cuproptosis-related molecular clusters in idiopathic pulmonary fibrosis disease.

Background: Idiopathic pulmonary fibrosis (IPF) has attracted considerable attention worldwide and is challenging to diagnose. Cuproptosis is a new form of cell death that seems to be associated with various diseases. However, whether cuproptosis-related genes (CRGs) play a role in regulating IPF disease is unknown. This study aims to analyze the effect of CRGs on the progression of IPF and identify possible biomarkers. Methods: Based on the GSE38958 dataset, we systematically evaluated the differentially expressed CRGs and immune characteristics of IPF disease. We then explored the cuproptosis-related molecular clusters, the related immune cell infiltration, and the biological characteristics analysis. Subsequently, a weighted gene co-expression network analysis (WGCNA) was performed to identify cluster-specific differentially expressed genes. Lastly, the eXtreme Gradient Boosting (XGB) machine-learning model was chosen for the analysis of prediction and external datasets validated the predictive efficiency. Results: Nine differentially expressed CRGs were identified between healthy and IPF patients. IPF patients showed higher monocytes and monophages M0 infiltration and lower naive B cells and memory resting T CD4 cells infiltration than healthy individuals. A positive relationship was found between activated dendritic cells and CRGs of LIPT1, LIAS, GLS, and DBT. We also identified cuproptosis subtypes in IPF patients. Go and KEGG pathways analysis demonstrated that cluster-specific differentially expressed genes in Cluster 2 were closely related to monocyte aggregation, ubiquitin ligase complex, and ubiquitin-mediated proteolysis, among others. We also constructed an XGB machine model to diagnose IPF, presenting the best performance with a relatively lower residual and higher area under the curve (AUC= 0.700) and validated by external validation datasets (GSE33566, AUC = 0.700). The analysis of the nomogram model demonstrated that XKR6, MLLT3, CD40LG, and HK3 might be used to diagnose IPF disease. Further analysis revealed that CD40LG was significantly associated with IPF. Conclusion: Our study systematically illustrated the complicated relationship between cuproptosis and IPF disease, and constructed an effective model for the diagnosis of IPF disease patients.

[Exploration and practice on construction of Tibetan medicine prescription information database and knowledge discovery].

This study aimed to explore the underlying framework and data characteristics of Tibetan prescription information. The information on Tibetan medicine prescriptions was collected based on 11 Tibetan medicine classics, such as Four Medical Canons(Si Bu Yi Dian). The optimal classification method was used to summarize the information structure of Tibetan medicine prescriptions and sort out the key problems and solutions in data collection, standardization, translation, and analysis. A total of 11 316 prescriptions were collected, involving 139 011 entries and 63 567 pieces of efficacy information of drugs in prescriptions. The information on Tibe-tan medicine prescriptions could be summarized into a "seven-in-one" framework of "serial number-source-name-composition-efficacy-appendix-remarks" and 18 expansion layers, which contained all information related to the inheritance, processing, origin, dosage, semantics, etc. of prescriptions. Based on the framework, this study proposed a "historical timeline" method for mining the origin of prescription inheritance, a "one body and five layers" method for formulating prescription drug specifications, a "link-split-link" method for constructing efficacy information, and an advanced algorithm suitable for the research of Tibetan prescription knowledge discovery. Tibetan medicine prescriptions have obvious characteristics and advantages under the guidance of the theories of "three factors", "five sources", and "Ro-nus-zhu-rjes" of Tibetan medicine. Based on the characteristics of Tibetan medicine prescriptions, this study proposed a multi-level and multi-attribute underlying data architecture, providing new methods and models for the construction of Tibetan medicine prescription information database and knowledge discovery and improving the consistency and interoperability of Tibetan medicine prescription information with standards at all levels, which is expected to realize the "ancient and modern connection-cleaning up the source-data sharing", so as to promote the informatization and modernization research path of Tibetan medicine prescriptions.

Exploration and practice on construction of Tibetan medicine prescription information database and knowledge discovery / 中国中药杂志

This study aimed to explore the underlying framework and data characteristics of Tibetan prescription information. The information on Tibetan medicine prescriptions was collected based on 11 Tibetan medicine classics, such as Four Medical Canons(Si Bu Yi Dian). The optimal classification method was used to summarize the information structure of Tibetan medicine prescriptions and sort out the key problems and solutions in data collection, standardization, translation, and analysis. A total of 11 316 prescriptions were collected, involving 139 011 entries and 63 567 pieces of efficacy information of drugs in prescriptions. The information on Tibe-tan medicine prescriptions could be summarized into a "seven-in-one" framework of "serial number-source-name-composition-efficacy-appendix-remarks" and 18 expansion layers, which contained all information related to the inheritance, processing, origin, dosage, semantics, etc. of prescriptions. Based on the framework, this study proposed a "historical timeline" method for mining the origin of prescription inheritance, a "one body and five layers" method for formulating prescription drug specifications, a "link-split-link" method for constructing efficacy information, and an advanced algorithm suitable for the research of Tibetan prescription knowledge discovery. Tibetan medicine prescriptions have obvious characteristics and advantages under the guidance of the theories of "three factors", "five sources", and "Ro-nus-zhu-rjes" of Tibetan medicine. Based on the characteristics of Tibetan medicine prescriptions, this study proposed a multi-level and multi-attribute underlying data architecture, providing new methods and models for the construction of Tibetan medicine prescription information database and knowledge discovery and improving the consistency and interoperability of Tibetan medicine prescription information with standards at all levels, which is expected to realize the "ancient and modern connection-cleaning up the source-data sharing", so as to promote the informatization and modernization research path of Tibetan medicine prescriptions.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

[Analysis of the principles of Tibetan medicine processing].

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.

Different expression of circulating microRNA profile and plasma SP-D in Tibetan COPD patients.

COPD is the fourth leading cause of mortality, and is predicted to be the third leading cause of death worldwide by 2020. But few studies on Tibetan COPD of China. This study identifies distinctive miRNA signatures in Tibetan COPD patients from Tibetan healthy subjects that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. In this study, a total of 210 differentially expressed miRNAs were screened. Analysis of the functions of target genes of differentially expressed miRNAs via GO enrichment analysis revealed that they mainly influenced guanyl-nucleotide exchange factor activity, cell morphogenesis and the positive regulation of GTPase activity. KEGG pathway enrichment analysis showed that these target genes were mainly enriched in signaling by NGF, Axon guidance, developmental biology, ubiquitin mediated proteolysis, and PDGF signaling pathways. MiR-106-5p and miR-486-5p expression was validated in the complete cohort. Age, plasma miR-106-5p, miR-486-5p, SP-D protein levels, and SP-D mRNA level were also determined to be correlated with FEV1%Pred, and may as the risk factors of Tibetan COPD. The combination of plasma miR-106-5p, miR-486-5p and SP-D mRNA expression may be the best model to assist the diagnosis of Tibetan COPD.

High-altitude hypoxia-induced rat alveolar cell injury by increasing autophagy.

Autophagy has been implicated in the pathogenesis of various lung diseases. This study aimed to investigate the role of autophagy in lung injury induced by high-altitude hypoxia. Wistar rats were randomized into four groups for exposure to normal altitude or high altitude for 1, 7, 14 and 21 days with no treatment or with the treatment of 1 mg/kg rapamycin or 2 mg/kg 3-methyladenine (3-MA) for consecutive 21 days respectively. In control rats, the alveolar structure was intact with regularly arranged cells. However, inflammatory cell infiltration and shrunk alveoli were observed in rats exposed to hypoxia. Rapamycin treatment led to many shrunken alveoli with a large number of red blood cells in them. In contrast, 3-MA treatment led to almost intact alveoli or only a few shrunken alveoli. Compared to the control group exposure to high-altitude hypoxia for longer periods resulted in the aggravation of the lung injury, the formation of autophagosomes with a double-membrane structure and increased levels of Beclin-1 and LC3-II in alveolar tissues. Rapamycin treatment resulted in significant increase in Beclin-1 and LC3-II levels and further aggravation of alveolar tissue damage, while 3-MA treatment led to opposite effects. In conclusion, exposure to high-altitude hypoxia can induce autophagy of alveolar cells, which may be an important mechanism of high-altitude hypoxia-induced lung injury. The inhibition of autophagy may be a promising therapy strategy for high-altitude hypoxia-induced lung injury.

Efficacy and Prognostic Analysis of 315 Stage I-IVa Esophageal Cancer Patients Treated with Simultaneous Integrated Boost-Intensity-Modulated Radiation Therapy.

PURPOSE: Use of simulated integrated boost-intensity-modulated radiation therapy (SIB-IMRT) is rarely reported in the treatment of esophageal cancer. This study was performed to observe the curative effect and prognostic factors associated with concurrent chemoradiotherapy for esophageal cancer using modern radiotherapy (RT) techniques. PATIENTS AND METHODS: In total, 315 patients with esophageal squamous cell carcinoma who received SIB-IMRT between 2015 and 2018 were included in this retrospective study. Median doses were planning target volume (PTV) 5400 cGy, 30 times (180cGy/fraction); planning gross tumor volume (PGTV) 6000 cGy, 30 times (200 cGy/fraction), once a day and 5 times a week. The entire period of RT was 6 weeks. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse reactions were observed. Univariate analysis was performed, and factors with P<0.15 were included in multivariate analysis. Cox regression analysis was used for multivariate prognostic analysis. P<0.05 was considered statistically significant. The incidence of adverse reactions under single chemotherapy concurrent chemoradiotherapy (sCCRT) and double chemotherapy concurrent chemoradiotherapy (dCCRT) was analyzed. RESULTS: Two-year, 3-year OS and PFS of the entire group were 49.5%, 40.2% and 40.3%, 34.0%, and the median survival time was 23.5 months. Univariate and multivariate analyses showed that T-stage (P=0.049), N-stage (P=0.024), clinical stage (P=0.041), short-term efficacy (P<0.001), and use of concurrent chemotherapy (P<0.001) were the influencing factors for OS. ORR was 87.6%. Adverse reactions were significantly increased with increasing chemotherapy dose. CONCLUSION: The adverse reactions of SIB-IMRT in esophageal cancer can be tolerated. T-stage, N-stage, clinical stage, short-term curative effect, and concurrent chemotherapy are the prognostic factors affecting survival. Because it has lower toxicity and is as effective as dCCRT, sCCRT should be considered in the management of esophageal cancer.

[Bioaccumulation and Translocation Characteristics of Heavy Metals in a Soil-Maize System in Reclaimed Land and Surrounding Areas of Typical Vanadium-Titanium Magnetite Tailings].

A total of 86 soil samples, 86 corn kernel samples, 50 tailings samples, and 33 ore rock samples were collected in reclaimed land and surrounding areas of typical vanadium-titanium magnetite tailings located in the Chengde Central Region and analyzed for 14 elements (P, Fe, Cu, Ni, Cd, Cr, Pb, Zn, Hg, Ti, Mn, and Mo) and speciation of heavy metals. This study investigated the bioaccumulation and translocation characteristics of heavy metals in a soil-maize system based on a descriptive statistical analysis, a geological accumulative index, bioconcentration factors, and a redundancy analysis. The results showed that the average accumulation index of surface soil followed an order of P > Cu > Fe2O3 > Cr > Ti > V > Ni > Mn > Cd > Zn > Mo > As > Pb > Hg, while the accumulation level of heavy metals was generally categorized as either no accumulation or moderate accumulation. Compared to China's soil environmental quality standard risk screening values (GB15618-2018), the over-standard rates of Cr and Cu were 2.32% and 1.16%, respectively. The content of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and surrounding areas was relatively high, and the content of Mo, Ni, Cu, Zn, Cd, and Cr in the control area was relatively high. The over-standard rates of Ni, Zn, and Cu in the corn kernels were 13.61%, 13.23%, and 5.17% respectively, according to China's national food safety standard limits for contaminants in food (GB 2762-2017). The bioconcentration factors of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and the surrounding areas were relatively higher, while the bioconcentration factors of Mo, Ni, Cu, Zn, Cd, and Cr were lower than in control area. The bioactive components of Cd accounted for 50.17%, which was the highest, followed by Ni, Zn, and Cu with average ratios of 13.61%, 13.23%, and 5.17%, respectively. Compared to the control area, the Pb, As and Hg elements in the soil samples of the reclaimed land showed a lower total amount but a higher bioavailability content and soil pH value, while the Cu and Hg elements showed a higher total amount but lower bioavailability content and soil pH value. These differences in total heavy metal concentrations, bioavailability amounts, and soil pH values made the bioconcentration intensity of As and Pb in the tailings reservoir and surrounding area relatively higher. When studying the ecological risk of heavy metal pollution or determining the remediation target value of reclaimed land in a mine tailings reservoir and the soil around the mine area, the bioavailable state limit of heavy metals should be should be taken into account as the evaluation standard.

Generic Association Analysis on "Prescription-Formula-Dosage-Property" of Tibetan Medicine Based on Partial Order Structure and Property Theory / 中国实验方剂学杂志

Objective:In view of the complexity of the "Prescription-Formula-Dosage-Property" relationship of Tibetan medicine and the outstanding common relationship，it is difficult to reveal the hidden and specific rules of clinical medication of Tibetan medicine. Method:Based on the attribute partial order structure and the vector structure model of "Ro-Nus-Zhu-Rjes"（Taste，Post-Digestive Tastes and Potency），clustering analysis and other methods and software，this study analyzed the "Prescription-Formula-Dosage-Property" relationship of 184 commonly used prescriptions in the 1995 edition of the standards issued by the Ministry of Tibetan medicine（SIMTM）. Result:Among them，the analysis of the relationship between prescription and formula found that 11 prescriptions with the largest common attribute，such as Chebulae Fructus and Carthami Flos，were the key components of classification and compatibility，which could effectively classify the 8 kinds of prescriptions for the treatment of lung disease，tripa disease and blood fever. Among them，the san Yin and auxiliary viscera function prescriptions，such as Sanguotang powder and Liuwei Liangyao powder，had the strongest commonality. According to the analysis of relationship between formula and dosage ，the dosage of Chebulae Fructus，Carthami Flos，pomegranate seed，Phyllanthi Fructus was the highest，which suggested that these drugs were often used as primary drugs，while the Liuwei Liangyao powder，such as Amomi Fructus Rotundus and Tsaoko Fructus，had a higher frequency but a lower dose，which mainly played a role in regulating the overall drug property of the prescription and protecting the viscera. The Tibetan medicine-specific drugs including Moschus，Bovis Calculus，and Zhaxun，which were used in a high frequency but very low dose，had the effect of enhancing the drug property and guiding the affected part. According to the analysis of the relationship between dosage and property，there were many prescriptions belonging to cool nature，accounting for 75.6%. It was found that 67 prescriptions did not conform to the efficacy due to their different dosage. Conclusion:There are many common components and common usages in Tibetan medicine prescriptions. If these common associations are not treated，it will lead to the result that all diseases take these common associations as the core，but the hidden key factors cannot be solved. Therefore，it is necessary to pay attention to sensitivity and specificity at the multi-dimensional level of "prescription-formula-dosage-property"，so as to reveal the clinical medication thought of Tibetan medicine more effectively.

[Source of Groundwater Nitrate in Luanping Basin Based on Multi-environment Media Nitrogen Cycle and Isotopes].

The multi-environment media of water, surface soil and vadose zone soil samples were collected in the upstream of Miyun Reservoir, in the Luanping Basin of Chengde City, Hebei Province. The aim was to identify the pollution source, ratio, spatial distribution, migration, and transformation characteristics of nitrogen in groundwater. Hydrogeochemistry, soil total nitrogen, and dissolved nitrate nitrogen of vadose zone soil analysis and a multi isotope tracer technique of δ15 N-NO3 and δ18O-NO3, δ34S-SO4 and δ18O-SO4, δ14 C, combined with land-use type analysis and geostatistics, were used in the study. The results showed that nitrate was the main form of nitrogen in the groundwater of the Luanping Basin. The NO3- concentration of groundwater was significantly correlated with the land-use types of residential land and cultivated land where the nitrate pollution of shallow groundwater was mainly distributed. Of the groundwater samples, 13.79% exceeded the National Standard Ⅲ for Groundwater (GB/T 14848-2017) of NO3- concentration value, while the excess multiple was 1.04-3.86, and 37.93% of the groundwater samples exceeded the World Health Organization NO3- concentration standard value. The excess multiple was 1.08-6.83. The spatial variation of groundwater NO3- concentration, soil total nitrogen and surface soil dissolved nitrate nitrogen of vadose zone was affected by the combination of natural structural factors and anthropogenic factors. The source of groundwater nitrate was mainly from livestock manure and domestic sewage, followed by chemical fertilizer leaching. The nitrogen cycle in the aeration zone-groundwater-dominated nitrogen circulation in the groundwater runoff area of the piedmont basin was nitrification. These findings are highly significant for the prevention and remediation of groundwater pollution when viewing the basin system as an independent unit, and for studying the sources and fate of nitrate pollution in the water environment.

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery.

Whole-breast radiotherapy after breast-conserving surgery (BCS) can improve patient survival while reducing local tumor recurrence. Although standard breast radiotherapy can achieve good tumor control and cosmetic effects with low toxicity, the 5- to 7-week treatment time is relatively long for patients and can result in wasted medical resources. Therefore, there is a growing trend toward hypofractionated radiotherapy (HFRT), which accelerates partial-breast irradiation. Both short-course radiotherapy and conventional fractionated radiotherapy are safe and effective treatment modes, with similar survival and local tumor control effects as those of conventional radiotherapy (CRT), and adverse reactions can be tolerated. Compared with conventional fractionated radiotherapy, short-course radiotherapy saves medical resources and has a shorter total treatment time, reduced treatment costs, and an improved quality of life for patients.

[Study on regularity of drug use in Tibetan medicine treating hypertension based on multi-center clinical medical records and "prescription-property-efficacy-disease"].

This study aimed to explore the rule of Tibetan medicine in clinical treatment of hypertension( k Hrag-rLung-stod-vtshangs) and analyze the characteristics of its prescriptions. One hundred and thirty-seven cases of hypertension treated Tibetan medicine were collected. Data mining,Gephi,Cytoscape and other methods and software were used to analyze the characteristics of Tibetan medicine. The results showed that there were 44 cases of r Lung-type hypertension in clinical medical records,while 57 cases of k Hrag-type hypertension. There were 103 treatment prescriptions. The frequency of these prescriptions covered Twenty-five Yuganzi Pills( 96 times),Seventy Pearl Pills( 80 times),Eight Chenxiang Pills( 75 times),and Sanwei Ganlu Powder( 62 times),and they were highly correlated,with confidence greater than 95%. There were 332 prescriptions involved in the prescriptions which is core prescription medicines. This study first proposed the dosage analysis method of Tibetan medicine prescription medicines,and obtained the more dosage of Chebulae Fructus,Phyllanthi Fructus,Aucklandiae Radix,Aquilariae Lignum Resinatum and so on. The correlation analysis of the prescription medicines found that Carthami Flos,Myristicae Semen,Bambusae Concretio Silicea,Caryophylli Flos,Amomi Fructus Rotundus led by Tsaoko Fructus had a high correlation and a confidence greater than 75%. These herbs were guaranteed when Tibetan medicine was used in combination. The key drugs for protecting viscera and regulating the three gastric fires. The prescription is mainly cold,blunt,sparse and rough. Its efficacy focuses on the pathogenesis of blood fever,blood stickiness and venous blockage caused by heat,sharpness,odor and stickiness. It mainly treats Tibetan medicine diseases such as k Hrag-r Lung-stod-vtshangs and k Hrag-vpel( polyemia). It is suggested that Tibetan medicine has a three-in-one invisible treatment principle of " clearing blood-heat,opening vessel and regulating stomach-fire" in the treatment of hypertension,which attributed to both cardiovascular function and gastrointestinal metabolic function. This may be a significant and invisible knowledge of Tibetan medicine in the treatment of hypertension.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Study on regularity of drug use in Tibetan medicine treating hypertension based on multi-center clinical medical records and "prescription-property-efficacy-disease" / 中国中药杂志

This study aimed to explore the rule of Tibetan medicine in clinical treatment of hypertension( k Hrag-rLung-stod-vtshangs) and analyze the characteristics of its prescriptions. One hundred and thirty-seven cases of hypertension treated Tibetan medicine were collected. Data mining,Gephi,Cytoscape and other methods and software were used to analyze the characteristics of Tibetan medicine. The results showed that there were 44 cases of r Lung-type hypertension in clinical medical records,while 57 cases of k Hrag-type hypertension. There were 103 treatment prescriptions. The frequency of these prescriptions covered Twenty-five Yuganzi Pills( 96 times),Seventy Pearl Pills( 80 times),Eight Chenxiang Pills( 75 times),and Sanwei Ganlu Powder( 62 times),and they were highly correlated,with confidence greater than 95%. There were 332 prescriptions involved in the prescriptions which is core prescription medicines. This study first proposed the dosage analysis method of Tibetan medicine prescription medicines,and obtained the more dosage of Chebulae Fructus,Phyllanthi Fructus,Aucklandiae Radix,Aquilariae Lignum Resinatum and so on. The correlation analysis of the prescription medicines found that Carthami Flos,Myristicae Semen,Bambusae Concretio Silicea,Caryophylli Flos,Amomi Fructus Rotundus led by Tsaoko Fructus had a high correlation and a confidence greater than 75%. These herbs were guaranteed when Tibetan medicine was used in combination. The key drugs for protecting viscera and regulating the three gastric fires. The prescription is mainly cold,blunt,sparse and rough. Its efficacy focuses on the pathogenesis of blood fever,blood stickiness and venous blockage caused by heat,sharpness,odor and stickiness. It mainly treats Tibetan medicine diseases such as k Hrag-r Lung-stod-vtshangs and k Hrag-vpel( polyemia). It is suggested that Tibetan medicine has a three-in-one invisible treatment principle of " clearing blood-heat,opening vessel and regulating stomach-fire" in the treatment of hypertension,which attributed to both cardiovascular function and gastrointestinal metabolic function. This may be a significant and invisible knowledge of Tibetan medicine in the treatment of hypertension.

Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: A meta-analysis.

BACKGROUND: The impact of high body mass index (BMI, >23/25 kg/m) on surgical outcomes and prognosis in patients with esophageal carcinoma (EC) after undergoing esophagectomy remains controversial. We herein conducted a systematic review and meta-analysis to determine the relationship between high BMI and surgical outcomes and prognosis in patients undergoing esophagectomy for EC. METHODS: The study search was conducted by retrieving publications from the PubMed, Embase, Web of Science, and CNKI (up to September 8, 2017). Nineteen studies with 13,756 patients were included in this meta-analysis. RESULTS: We found that high BMI was closely associated with a higher incidence of wound infection (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.97, P = .04), cardiovascular complications (OR: 2.51, 95% CI, 1.65-3.81, P < .0001), and anastomotic leakage (OR: 1.50, 95% CI, 1.21-1.84, P = .0002), but a lower incidence of chylous leakage (OR: 0.59, 95% CI, 0.40-0.88, P = .01) when compared with normal BMI. The high BMI group was not associated with better or worse overall survival (OS) (hazard ratio [HR]: 0.95, 95% CI, 0.85-1.07, P = .4) and disease-free survival (HR: 0.95, 95% CI, 0.72-1.25, P = .72) than the normal BMI group. However, in the subgroup analysis, the pooled result of HRs generated from multivariate analyses suggested that high BMI could improve OS in EC patients (HR: 0.84, 95% CI, 0.76-0.93, P < .01). CONCLUSIONS: Overweight patients with EC should not be denied surgical treatment, but intraoperative prevention and careful postoperative monitoring for several surgical complications must be stressed for this population. Besides, high BMI might be a prognostic predictor in EC patients; further studies are warranted.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.