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Assessing collective drug consumption based on the species and concentrations of illicit drugs and their metabolites in wastewater is an objective, real-time, accurate, convenient and effective monitoring technology. In order to establish a rapid screening and confirmation method for the abuse of opioids, amphetamines and benzodiazepines in wastewater, solid phase extraction was used to pretreat the wastewater sample, and ultra-high liquid chromatography tandem high resolution mass spectrometry was used to screen and confirm 36 kinds of analytes. Moreover, the method was applied to real wastewater samples collected from different wastewater treatment plants. Different HPLC columns and mobile phases were tested for optimization of the method. The peak shapes, retention time, separation and sensitivity of the chromatographic procedure were evaluated. Finally, an Accucore Hypersil Gold column (100 mm×2.1 mm×1.9 μm), and the mobile phases of ultrapure water with 2 mmol/L ammonium formate 0.1%-formic acid (A) and acetonitrile-methanol (1∶1, V/V) with 2 mmol/L ammonium formate and 0.1% formic acid were applied because of good peak shapes and separation. TraceFinder software was selected for rapid screening, and retention time, molecular mass, fragment ions and isotope distribution were collected as the screening basis. A substance could be judged as positive if it all met these 4 screening conditions. Therefore, the results obtained were more authentic and reliable. The LODs ranged from 5 to 20 ng/L. The extraction recoveries were higher than 70% for all compounds in wastewater, and the matrix effect ranged from -24.4% to 21.2%. In the real wastewater samples, 4 opioids of morphine, codeine, pethidine, tramadol, 1 amphetamine of methamphetamine and 4 benzodiazepines of diazepam, nordazepam, estazolam, alprazolam were detected, and the error of all compounds were less than 5×10-6. There are many kinds of abused substances in wastewater, and the regional prevalence is also different. The method established in this article can be used for rapid and accurate screening and confirmation abused substances in wastewater.

Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.

Background Methods Results Conclusions Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial.We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis.After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients.The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization. [ABSTRACT FROM AUTHOR]

This study explored the active ingredients and mechanism of action of Crataegi Fructus in the treatment of coronary heart disease through network pharmacology and molecular docking technology. With the help of TCMSP, Gene Cards, OMIM and other databases to collect target information, the STRING database was used to construct a PPI network diagram, perform GO and KEGG pathway enrichment analysis on the common target, and finally molecularly dock the active ingredient with the core target to initially verify the network pharmacology results. In this study, a total of 6 Crataegi Fructus active ingredients (sitosterol, kaempferol, stigmasterol, quercetin, ent-Epicatechin, isorhamnetin) and 10 Crataegi Fructus core targets for the treatement of coronary heart disease (JUN, AKT1, TNF, MAPK1, TP53, RELA, IL6, MAPK8, MAPK14, EGFR) were screened; KEGG pathway enrichment results showed that Crataegi Fructus prevention and treatment of coronary heart disease pathway involved pathway in cancer, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, MAPK signaling pathway, etc.; Molecular docking results showed that quercetin, isorhamnetin and kaempferol all had good binding to the core target. It is speculated that these components may be the main active components for the treatment of coronary heart disease. This study revealed that Crataegi Fructus may treat coronary heart disease through multiple components (isorhamnetin, kaempferol, quercetin), acting on key targets such as MAPK8, MAPK1, RELA, and regulating multiple signaling pathways such as MAPK. It preliminarily revealed the potential mechanism of Crataegi Fructus in the treatment of coronary heart disease.

Edge bundling is an effective method to reduce the visual clutter caused by the visualization of the node-link diagram with a large number of complex connections.Generally,the edge bundling based on spatial proximity will lead to independent edge ambiguity and give users a wrong perception.However,focusing only on topological structure of graphs cannot reduce visual clutter caused by dense connections to a large extent.The method based on edge path can control and bundle the edges by using the original nodes in the graph,avoid independent edge ambiguity,and show the advanced mode of data.Therefore,an edge bundling method based on homologous control points is proposed to improve the edge path method.Based on the topology structure information of the graph,the method can calculate homologous control points and select edge control points by using the shortest path algorithm.Then the degree of edge aggregation is optimized with the thinking of gradation.Finally,the edges are smoothed through Bezier curves and colored according to the direction of the edges.The edge bundling method based on homologous control points is used in the US migration dataset and the Chinese railway line dataset.Experimental results show that this method has a good effect on improving the problem of over-bundling.Compared with the original method,this method retains more local data details,balances the bundling degree between the whole and local edges,and can be effectively used for the visualization of complex connected graphs.