A Rare Case Report of Disseminated Nocardia Farcinica Granulomatous Hepatitis and Clinical Management Experience.

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

Angioplasty for Supra-Aortic Arterial Lesions from Takayasu Arteritis: Efficacy of Cutting Balloon Angioplasty Versus Conventional Balloon Angioplasty.

BACKGROUND: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis. METHODS: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups. RESULTS: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively. CONCLUSIONS: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit.

CXCR4 inhibitor, AMD3100, down-regulates PARP1 expression and Synergizes with olaparib causing severe DNA damage in BRCA-proficient triple-negative breast cancer.

Poly ADP-ribose polymerase inhibitor (PARPi) treatment is effective in triple-negative breast cancer (TNBC) with BRCA mutation. However, its efficacy in BRCA-proficient TNBC remains unexplored. It is, therefore, an exciting proposition to broaden the indication of PARPi for BRCA-proficient TNBC patients. Chemokine receptor (CXCR4) is a transmembrane G protein-coupled receptor, which is involved in cell migration, proliferation, apoptosis, and damage repair, and it initiates many signalling pathways. Although administration of CXCR4 inhibitor alone is not ideal as a target drug, it can play a strong synergistic role in combination with other drugs. We explored the effect of CXCR4 and PARP1 on tumour cell proliferation, migration, metastasis, and apoptosis in vitro and in vivo and found that a CXCR4 inhibitor, AMD3100, enhanced the anti-tumour effect of PARP1 inhibitor, olaparib, on BRCA-proficient TNBC. When CXCR4 was inhibited and silenced, DNA damage repair and DNA replication fork activity were suppressed by up-regulating caspase-3-mediated increase in PARP1 cleavage; in combination with the inhibition of PARP1, AMD3100 resulted in the accumulation of fatal DNA damage and induction of apoptosis. This combination regimen can be effective against BRCA-proficient TNBC.

Small Unruptured Intracranial Aneurysms Can Be Effectively Treated With Flow-Diverting Devices.

Purpose: To investigate the effect and safety of flow diverters in the management of small (<10 mm in diameter) unruptured intracranial aneurysms. Materials and Methods: One hundred and ten patients with 145 small intracranial aneurysms treated with flow diverters were retrospectively enrolled. The clinical, endovascular, and follow-up data were analyzed. Results: One hundred twenty-one flow diverters were deployed for the treatment of 145 small intracranial aneurysms in 110 patients, and the stenting success rate was 99.1%. In 133 (91.7%) aneurysms, only flow-diverting devices were deployed, and in the rest 12 (8.3%) of aneurysms, coils were used to loosely pack the aneurysm after deployment of a flow-diverting device. Five patients (4.5%) experienced ischemic complications, but no hemorrhagic complications were occurred. All patients had clinical follow-up 6-18 (median 12) after the procedure, with the modified Rankin scale score (mRS) 0 in 101 patients, 1 in four patients, 2 in three patients, 4 in one patient, and 5 in one patient. Digital subtraction angiography was performed at follow-up in 90 (81.8%) patients with 118 (81.4%) aneurysms 6-18 months (median 12) after the procedure, with the Raymond grade I in 90 (76.2%) aneurysms and Raymond grade III in 28 (23.7%). Eighteen patients with 22 partially occluded aneurysms at the first angiographic follow-up experienced the second digital subtraction angiography 12-36 months (median 26) after the procedure, and 21 (95.5%) aneurysms were completely occluded. Two patients had asymptomatic in-stent stenosis. Conclusion: Treatment of small unruptured intracranial aneurysms with flow diverters can be performed safely and effectively with satisfactory outcomes.

C-reactive protein to albumin ratio predicts the outcome in renal cell carcinoma: A meta-analysis.

BACKGROUND: Growing evidence has revealed that pretreatment C-reactive protein to albumin ratio (CAR) are associated with prognosis for patients with renal cell carcinoma (RCC). However, inconsistent findings have been reported, which promote us to summarize the global predicting role of CAR for survival in RCC patients. METHODS: Two reviewers independently retrieved the literature on EMBASE, MEDLINE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival. Data related to the overall survival (OS), disease-free survival (DFS), progress-free survival (PFS), and clinicopathological features were extracted and pooled using meta-analysis with fixed or random- effect models when applicable. RESULTS: Eight studies including 2,829 patients were analyzed in the present study. High pretreatment CAR was associated with worse OS (pooled HR: 2.14, 95% CI = 1.64-2.79, p < 0.001) and DFS/PFS (pooled HR: 1.75, 95% CI: 1.31-2.35, P < 0.001). Moreover, high CAR was correlated with performance status (≥ 1), tumor location (left), Fuhrman grade (3-4), TNM stage (III-IV), T stage (T3-4), N stage (N1), M stage (M1), tumor necrosis (yes), venous thrombus (positive), metastasis at diagnosis (yes), NLR (> median), and PLR (> median). CONCLUSION: High pretreatment CAR is effectively predictive of worse survival in patients with RCC and could be a prognostic biomarker for those patients.

A Model for the Prediction of Survival in Patients With Upper Tract Urothelial Carcinoma After Surgery.

OBJECTIVE: We aimed to formulate and validate prognostic nomograms that can be used to predict the prognosis of patients with upper tract urothelial carcinoma (UTUC). METHODS: By consulting the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients who were surgically treated for UTUC between 2004 and 2013. Variables were analyzed in both univariate and multivariate analyses. Nomograms were constructed based on independent prognostic factors. The prognostic nomogram models were established and validated internally and externally to determine their ability to predict the survival of patients with UTUC. RESULTS: A total of 4990 patients were collected and enrolled in our analyses. Of these, 3327 patients were assigned to the training set and 1663 to the validation set. Nomograms were effectively applied to predict the 3- and 5-year survivals of patients with UTUC after surgery. The nomograms exhibited better accuracy for predicting overall survival (OS) and cancer-specific survival (CSS) than the tumor-node-metastasis (TNM) staging system and the SEER stage in both the training and validation sets. Calibration curves indicated that the nomograms exhibited high correlation to actual observed results for both OS and CSS. CONCLUSIONS: The nomogram models showed stronger predictive ability than the TNM staging system and the SEER stage. Precise estimates of the prognosis of UTUC might help doctors to make better treatment decisions.

Perovskite-Like Organic-Inorganic Hybrid Lead Iodide with a Large Organic Cation Incorporated within the Layers.

A great effort has been made to investigate 2D perovskites to improve the stability and controllability in the fabrication of photoelectronic devices. As far as we know, only small organic cations such as methylammonium can incorporate into the multilayered perovskite structure except the cations sandwiched between the inorganic layers. We report here a new layered lead iodide, (H2Aepz)3Pb4I14 (1), where larger organic cations, bis-protonated 2-(2-aminoethyl)pyrazole (Aepz), not only were sandwiched between the inorganic layers but also were incorporated within the perovskite-like PbI layered structure. Another 2D compound, (H2Aepz)PbI4 (2), was also prepared that was a one-layer perovskite. A simple Schottky device was prepared to investigate the photoelectroresponsive properties of the compounds in comparison with that of a typical organic-inorganic hybrid perovskite. In general, the energy gap is decreased with an increase in the perovskite layers, but the band gap of two-layered 1 is larger than that of one-layered 2. The photocurrent densities of the compounds are in the order of 1 < 2 < (CH3NH3)PbI3, which is discussed based on the crystal structures and band energy gaps.

A lanthanide-titanium (LnTi11) oxo-cluster, a potential molecule based fluorescent labelling agent and photocatalyst.

Although a lot of titanium oxo-clusters (TOCs) have been synthesized and characterized, research studies on their application properties are still limited. The work described here is not only aimed at the synthesis and crystal structures of the TOCs, but also aimed at exploration of their potential applications in molecule based fluorescence labelling and photocatalysis. Three heterometallic TOC compounds with lanthanide (Ln) elements Sm(iii) (1), Eu(iii) (2) and Gd(iii) (3) are prepared and their cluster structures are characterized as LnTi11 cages. Compound 2 exhibits the characteristic fluorescence of Eu(iii) and the emission intensity can be decreased upon irradiation and recovered by air oxidation, which is attributed to the energy transfer between Eu(iii) and photo-induced Ti(iii) of the oxo-TiO cluster. The fluorescence intensity of 2 can be significantly increased when treated with 1,10-phenanthroline. The catalytic properties of 2 were determined by the degradation of dyes on a paper substrate. Compound 2 has potential applications as a molecule based fluorescent labelling agent and photodegeneration catalyst.

Binding of human recombinant mutant soluble ectodomain of FGFR2IIIc to c subtype of FGFRs: implications for anticancer activity.

FGFRs are considered essential targets for cancer therapy. We previously reported that msFGFR2c, a Ser252Trp mutant soluble ectodomain of FGFR2IIIc, inhibited tumor growth by blocking FGF signaling pathway. However, the underlying molecular mechanism is still obscure. In this study, we reported that msFGFR2c but not wild-type soluble ectodomain of FGFR2IIIc (wsFGFR2c) could selectively bind to c subtype of FGFRs in the presence of FGF-2. Thermodynamic analysis demonstrated that msFGFR2c bound to wsFGFR2c in the presence of FGF-2 with a K value of 6.61 × 105 M-1. Molecular dynamics simulations revealed that the mutated residue Trp252 of msFGFR2c preferred a π-π interaction with His254 of wsFGFR2c. Concomitantly, Arg255 of msFGFR2c and Glu250 of wsFGFR2c adjusted their conformations and formed three H-bonds. These two interactions therefore stabilized the final structure of wsFGFR2c and msFGFR2c heterocomplex. In FGFR2IIIc-positive/high FGF-2-secreted BT-549 cells, msFGFR2c significantly inhibited the proliferation and induced apoptosis by the blockage of FGF-2-activated FGFRs phosphorylation, also the growth and angiogenesis of its xenograft tumors implanted in chick embryo chorioallantoic membrane model. While weaker the above inhibitory effects of msFGFR2c were observed on FGFR2IIIc-negative/low FGF-2-secreted MCF-7 and MDA-MB-231 cell lines in vitro and in vivo. Moreover, msFGFR2c significantly inhibited the proliferation of FGFR1IIIc-positive NCI-H1299 lung cancer cells by the suppression of FGF-2-induced FGFR1 activation and suppressed the growth of NCI-H1299 transplanted tumors in nude mice. In sum, msFGFR2c is a potential anti-tumor agent targeting FGFR2c/FGFR1c-positive tumor cells. These findings also provide a molecular basis for msFGFR2c to disrupt the activation of FGF signaling.

Two Ti13-oxo-clusters showing non-compact structures, film electrode preparation and photocurrent properties.

Two benzene dicarboxylate (BDC) and salicylate (SAL) substituted titanium-oxo-clusters, Ti13O10(o-BDC)4(SAL)4(O(i)Pr)16 (1) and Ti13O10(o-BDC)4(SAL-Cl)4(O(i)Pr)16 (2), are prepared by one step in situ solvothermal synthesis. Single crystal analysis shows that the two Ti13 clusters take a paddle arrangement with an S4 symmetry. The non-compact (non-sphere) structure is stabilized by the coordination of BDC and SAL. Film photoelectrodes are prepared by the wet coating process using the solution of the clusters and the photocurrent response properties of the electrodes are studied. It is found that the photocurrent density and photoresponsiveness of the electrodes are related to the number of coating layers and the annealing temperature. Using ligand coordinated titanium-oxo-clusters as the molecular precursors of TiO2 anatase films is found to be effective due to their high solubility, appropriate stability in solution and hence the easy controllability.

Methyl methanesulfonate induces apoptosis in p53-deficient H1299 and Hep3B cells through a caspase 2- and mitochondria-associated pathway.

Methyl methanesulfonate (MMS) has been shown to induce apoptosis in various cell types through p53-dependent pathways. Nevertheless, pharmacological and genetic blockade of p53 functions results in similar or delayed sensitivity to MMS treatment, suggesting the presence of p53-independent apoptotic mechanisms. To understand the p53-independent mechanisms that are engaged during MMS-induced apoptosis, we established MMS-induced apoptotic cell models using p53-deficient H1299 and Hep3B cells. Our results demonstrated that MMS at concentrations of 50, 100, 200, 400 and 800 µM induced the formation of gammaH2AX foci, and that at higher concentrations, 400 and 800 µM, MMS treatment led to apoptosis in the two cell lines. This apoptotic cell death was concurrent with the loss of mitochondrial membrane potential, nuclear-cytosolic translocation of active caspase 2, release of cytochrome c from mitochondria, and the cleavage of caspase 9, caspase 3 and PARP. However, MMS-induced DNA damage failed to stabilize the p53 family members TAp73 and DNp73. These results demonstrated a p53- and p73-independent mechanism for MMS-induced apoptosis that involves the nuclear-cytosolic translocation of active caspase 2 as well as the mitochondria-mediated pathway.

A panel of five circulating microRNAs as potential biomarkers for prostate cancer.

BACKGROUND: Circulating microRNA (miRNAs) have been shown to have the potential as noninvasive diagnosis markers in several types of cancers. In this study, we investigated whether circulating miRNAs could be used in the diagnosis of prostate cancer (CaP) in a Chinese patient population. METHODS: Illumina's Human v2 miRNA microarray was used to analyze miRNAs levels in a small set of patients [25 CaP, 17 benign prostatic hyperplasia (BPH)] in an effort to identify CaP-specific miRNAs. The identified miRNAs were further examined by quantitative real-time PCR (qRT-PCR) in the same small set of patients. After the training phase of screening and selecting, the candidate miRNAs were validated in a larger independent cohort (80 CaP, 44 BPH, and 54 healthy controls) with qRT-PCR in the verification phase. RESULTS: Five miRNAs were confirmed by qRT-PCR analysis in validation sets. Receiver operating characteristic (ROC) curve analysis showed all 5 miRNAs had diagnostic value. More importantly, further principal component analysis indicated component 1 extracted from expression data of the 5 miRNAs could differentiate CaP from BPH and healthy controls with high diagnosis performance, with an AUC of 0.924 and 0.860, respectively. CONCLUSIONS: Our data suggested that circulating miRNAs could serve as biomarkers for CaP, and compared to single miRNA, the 5 miRNAs panel can accurately discriminate CaP from BPH and healthy controls with high sensitivity and specificity, and therefore, combined with routine PSA test, these 5 CaP-specific miRNAs may help improve CaP diagnosis in clinical application.

Membrane resonance and its ionic mechanisms in rat subthalamic nucleus neurons.

The oscillatory activity in the basal ganglia is believed to have an important function, but little is known about its actual mechanisms. We studied the resonance characteristics of subthalamic nucleus (STN) neurons and their ionic mechanisms using whole-cell patch-clamp recordings in rat brain slices. A swept-sine-wave current with constant amplitude and linearly increasing frequency was applied to measure the resonance frequency (f(res)) of STN neurons. We also used single-frequency sine wave current to evoke firing. We found that the resonance of STN neurons was temperature- and voltage-dependent. The f(res) of STN neurons was about 4Hz when the temperature was maintained at 38°C and holding potential was at -70mV. The f(res) increased with more negative holding potentials and decreased with lower temperature. Action potentials fired most readily when the input frequency was near f(res). After application of drug ZD7288 (20µM), the resonance of STN neurons was blocked and the spikes evoked by both impedance amplitude profile (ZAP) current and single-frequency sine wave current arose readily at the lowest frequencies, indicating that hyperpolarization-activated cation current (I(h)) generated the resonance and mediated a preferential coupling at frequencies near f(res) between inputs and firing. In conclusion, there is a θ-frequency resonance mediated by I(h) in STN neurons. The resonance characteristics are temperature- and voltage-dependent. The resonance mediates a frequency-selective coupling between inputs and firing.

Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation.

Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, a widely reputed medicinal plant in China, has been reported to have some neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague-Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and spatial learning and memory were assessed using the Morris water maze. Antioxidative capability was measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities, decrease lipid peroxide products and oxidative DNA damage, and reduce the activation of inflammatory astrocytes. However, GP 100 mg/kg had no significant effects. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

[Synthesis, spectral characterization and bioactivity of complexes of furoylpyrazolone-thiosemicarbazone].

A new Schiff base containing sulphur, 1-phenyl-3-methyl-4-(alpha-furoyl) pyrazolone-5-thiosemicarbazone (HL) and its Zn(II), Cd(II) and Co(II) complexes have been synthesized. On the basis of elemental analysis and molar conductance, the general formulae of the complexes, [ZnL2] x 1.5H2O, [CdL2] x C2H5OH and [CoL2] x H2O, were given. They were characterized by IR, UV-Visible, 1H NMR, 13C NMR and magnetic moments. The results show that the metal ions exhibit coordination of six in the complexes. The antibacterial experiments indicate that they have high antibacterial activities against S. aureus, B. subtilis, E. coli, E. carotovora, and C. flaccumfaciens.