["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Acute Colonic Pseudo-Obstruction in Severe Falciparum Malaria: A Case Report.

Severe falciparum malaria is associated with multiple organ dysfunctions. The most manifestations of severe falciparum malaria are cerebral malaria, acute lung injury, and acute kidney injury. Acute colonic pseudo-obstruction is extremely rare. Early recognition and management are essential because a delay in diagnosis is associated with substantial morbidity and mortality. A 29-year-old peacekeeper in the Democratic Republic of Congo (DRC) was diagnosed as severe falciparum malaria with high-grade fever, jaundice, electrolyte disturbance, and thrombocytopenia. Although adequate antimalaria therapy with intramuscular artemether was given, the patient had persistent fever, shallow and fast breathing, and abdominal pain. Investigations suggested a diagnosis of acute colonic pseudo-obstruction. Antimalarial therapy was continued with intravenous artesunate. And rectal decompression and fasting were taken. Soon, symptoms of colonic obstruction mitigated. And the patient was cured and discharged. Acute colonic pseudo-obstruction should be considered for severe malaria patients with abdominal distention and pain. The early diagnosis and proper management of the patient with severe malaria complicated with acute colonic pseudo-obstruction are the keys to a good prognosis.

Malignant fibrous histiocytoma of the bone in a traumatic amputation stump: A case report and review of the literature.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas among adults. It is characterized by large size, high grade, and biological aggressiveness. There are many reports of MFH after local stimulation, such as bone fracture, implants, and chronic osteomyelitis. In this paper, we report a patient who developed MFH 6 years after amputation, suggesting that wound healing and mechanical force play a role in the local stimulation of this disease. CASE SUMMARY: A 66-year-old man complained of persistent pain in his residual mid-thigh. He had undergone amputation surgery due to a traffic accident 6 years prior. Physical examination showed tenderness but no abnormalities in appearance. X-ray radiographs and magnetic resonance imaging supported the diagnosis of a tumor, and a biopsy confirmed that the lesion was MFH. The patient received neoadjuvant chemotherapy and left hip disarticulation. During the 6-mo follow-up, there were no symptoms of recurrence. CONCLUSION: Postsurgery MFH has been reported before, and many studies have attributed it to the biological effects of implants. Our case report shows that this disease can develop without an implant and thus highlights the importance of local stimulation. The wound-healing process and mechanical force can both promote this tumor, but whether they directly cause MFH needs further investigation.

A novel sandwich shaped {CoCoMo} cluster with a Co triangle encapsulated in two capped CoIIICoMoO40 fragments.

A novel discrete {Co14Mo24} nanoscale cluster, {CoIII2CoII10Cl2(dpbt)3(H2O)2[CoIIMoV12O31(CH3O)9]2}·24CH3OH (1) (here, dpbt = 5,5'-di(pyridin-2-yl)-3,3'-bi(1,2,4-triazole)), with a triangular Co4 core encapsulated in two novel capped Co-substituted Keggin-type Co5Mo12O40 anions, has been isolated from alkaline methanol solution. The high-resolution electrospray ionization mass spectrum (HRESI-MS) of microcrystalline 1 in MeOH/CH2Cl2 (v : v = 2 : 1) was recorded. Two prominent overlapping peaks in the range of m/z = 2740-2840 and 1820-1880 for the discrete fragments of [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)18-x-2H]2- (x = 9-18, F1) and [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)19-x-2H]3- (x = 6-13, F2), respectively, are obtained, confirming the {Co14Mo24} composition in 1. In addition, weak anti-ferromagnetic interactions in 1 are observed.

In vitro and in vivo antitumor activities of three novel binuclear platinum(II) complexes with 4'-substituted-2,2':6',2″-terpyridine ligands.

Herein, we report the design and synthesis of three novel binuclear platinum(II) complexes, [Pt(tpbtpy)Cl][Pt(DMSO)Cl3] (tpbtpy-Pt), [Pt(dthbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (dthbtpy-Pt), and [Pt(qlbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (qlbtpy-Pt) with 4'-(3-thiophenecarboxaldehyde)-2,2':6',2″-terpyridine (tpbtpy), 4'-(3,5-bis (1,1-dimethylethyl)-2-hydroxy-benzaldehyde)-2,2':6',2″-terpyridine (dthbtpy) and 4'-(2-quinolinecarboxaldehyde)-2,2':6',2″-terpyridine (qlbtpy) as ligands, respectively. All three novel binuclear platinum(II) complexes tpbtpy-Pt, dthbtpy-Pt, and qlbtpy-Pt were characterized by single-crystal X-ray diffraction analysis, spectroscopic analysis (ESI-MS, IR, 1H NMR), and elemental analysis. Additionally, the cytotoxicity of tpbtpy-Pt, dthbtpy-Pt and qlbtpy-Pt was assessed with human non-small cell lung cancer cell line (NCIH460 cells), yielding IC50 values in the range of 0.35-12.09 µM with tpbtpy-Pt as the most potent and qlbtpy-Pt as the least potent complexes. Mechanistic studies indicated that tpbtpy-Pt and dthbtpy-Pt induced apoptosis through mitochondrial dysfunction and telomerase inhibition. In a NCIH460 xenograft model, when administered at 10.0 mg kg-1 every 2 days, tpbtpy-Pt was shown to significantly reduce tumor growth (tumor growth inhibition rate (IR) = 70.1%, p < 0.05). Therefore, tpbtpy-Pt is a promising Pt(II) complex for further translational studies and clinical evaluation as an antitumor agent.

Novel tacrine platinum(II) complexes display high anticancer activity via inhibition of telomerase activity, dysfunction of mitochondria, and activation of the p53 signaling pathway.

In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CH3OH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)] (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'-dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10-phenanthroline (PTH), 2-(1-pyrenecarboxaldehyde) imidazo [4,5-f]-[1,10] phenanthroline (PIPTH), 2-picolylamine (PM) and 1,2-ethylenediamine (en) as telomerase inhibitors and p53 activators. Biological evaluations demonstrated that Pt1Pt7 exhibited cytotoxic activity against the tested NCIH460, Hep-G2, SK-OV-3, SK-OV-3/DDP and MGC80-3 cancer cell lines, with Pt5 displaying the highest cytotoxicity. Pt5 exhibited an IC50 value of 0.13 ±â€¯0.16 µM against SK-OV-3/DDP cancer cells and significantly reduced tumor growth in a Hep-G2 xenograft mouse model (tumor growth inhibition (TGI) = 40.8%, p < 0.05) at a dose of 15.0 mg/kg. Interestingly, Pt1Pt7 displayed low cytotoxicity against normal HL-7702 cells. Mechanistic studies revealed that these compounds caused cell cycle arrest at the G2/M and S phases, and regulated the expression of CDK2, cyclin A, p21, p53 and p27. Further mechanistic studies showed that Pt5 induced SK-OV3/DDP cell apoptosis via dysfunction of mitochondria, inhibition of the telomerase activity by directly targeting the c-myc promoter, and activation of the p53 signaling pathway. Taken together, Pt5 has the potential to be further developed as a new antitumor drug.

Hierarchical Assembly of a {Co24} Cluster from Two Vertex-Fused {Co13} Clusters and Their Single-Molecule Magnetism.

We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co13(µ3-OH)3(µ3-Cl)(dpbt)5(ptd)Cl10][Co(H2O)2Cl2]·(CH3)2CHOH (1) and [Co24(µ3-OH)6(µ3-Cl)2(dpbt)10(ptd)2Cl16]·2CH3CH2OH (2), respectively (H2dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H2ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co4(µ3-OH)3(µ3-Cl)] cubane and an outer [Co9(dpbt)5(ptd)Cl10] defective adamantane. Compound 2 reveals a giant {Co24} cluster possessing a dual-[Co12] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).

An intuitional hierarchical assembly of cluster-organic frameworks with a thickness of 1.97 nm from a discrete Co14 cluster.

An intuitional hierarchical assembly, metaphorically referred to as a "blossom and yield fruit" process, from a discrete cluster {[Co14(CH3O)4(dpbt)6Cl12]·14CH3OH, ()} to 2D cluster organic frameworks {[Co14(CH3O)10(dpbt)6 Cl6]·12CH3OH, ()}, has been established. The magnetic ordering of was obviously improved compared with .

Solvent effects on the structures and magnetic properties of two doubly interpenetrated metal-organic frameworks.

Two doubly interpenetrated coordination polymers [Co2(BDC)2(bpt)2]·nSolvent based on dimeric secondary building units and crystallizing with distinct solvent molecules (-H2O and -MeOH for nSolvent = 2H2O and MeOH·H2O, respectively) were obtained by employing 1,4-benzenedicarboxylate (BDC) and 1H-3,5-bis(4-pyridyl)-1,2,4-triazole) (bpt) as linkers. The structures consist of a square grid of dimers bridged by BDC and pillared by bpt. Thermogravimetry and PXRD indicate that the frameworks are stable and are retained up to 400 °C, but the structures are modified irreversibly. -H2O, high-symmetry Pna21, exhibits antiferromagnetic coupling within the dimer, while -MeOH, low-symmetry P21/n, exhibits ferromagnetic coupling. Upon desolvation, the -de and -de couplings are antiferromagnetic but reduced. Subsequent resolvation to -H2O and -MeOH resulted in a slight increase of the antiferromagnetic coupling without attaining the virgin states. The interesting difference of magnetic properties between -H2O and -MeOH, the solvated/desolvated phases, particularly at low temperature, indicates that there is a prominent solvent effect.

Safety and long-term efficacy of endovascular treatment of small posterior communicating artery aneurysms by coiling with or without stent: a single center retrospective study.

OBJECTIVES: Endovascular stents have been widely used in intracranial aneurysm embolization. In this work, we compared the safety and long-term efficacy of stent-assisted coiling with those of conventional coiling for small posterior communicating artery aneurysms, aiming at a better understanding of the related safety and efficacy profiles. METHODS: Between January 2008 and December 2011, 114 small PcomA aneurysms (defined as 3mm≤maximum diameter<10mm in this study) in 108 patients were treated by endovascular treatment in our department. Patient demographics, aneurysm characteristics, angiographic results (initial and follow-up), and procedural complications were assessed. RESULTS: Embolization was successfully performed in all the patients. Complications occurred in 7.4% of patients in both groups. There was no associated mortality. Based on initial post-procedural angiography, the rate of complete aneurysm occlusion, neck remnant and residual sac in the stented group were 37.9%, 24.1%, and 37.9%, while in the conventional group the figures were 42.9%, 48.2%, and 8.9%, respectively. The initial angiographic results were significantly better in the conventional group, compared with the stented group (P=0.038). The follow-up results showed that the rate of improvement in the stented group was significantly higher (53.3% vs. 14.0%; P<0.001) and the recurrence rate was significantly lower than that in the conventional group (4.4% vs. 3.02%; P=0.001). CONCLUSION: Compared with conventional coiling, stent-assisted coiling of the small posterior communicating artery aneurysms does not increase the risk. Stents bear an advantage in reducing the recurrence rate, increasing progressive occlusion rate, and improving long-term prognosis in endovascular treatment of intracranial aneurysms.