Visible-Light-Induced Cascade Cyclization of 3-(2-(Ethynyl)phenyl)quinazolinones to Phosphorylated Quinolino[2,1-b]quinazolinones.

3-(2-(Ethynyl)phenyl)quinazolinones were designed and synthesized as a class of novel and efficient skeletons for phosphorylation/cyclization reactions. Under visible light irradiation, a series of phosphorylated quinolino[2,1-b]quinazolinones (35 examples, up to 87% yield) were first synthesized from 3-(2-(ethynyl)phenyl)quinazolinones and diarylphosphine oxides by using 4CzIPN as a photocatalyst under mild conditions. This reaction was also applicable under sunlight irradiation. Moreover, the reaction efficiency could be significantly improved under continuous-flow conditions.

Genetics of Severe Cutaneous Adverse Reactions.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Advances in identification of multiple genetic alleles associated with specific drugs related SCARS in different populations is an important breakthrough in recent years for prevention of SCARs. This article summarized the findings on genetic factors related to SJS/TEN, especially for HLA.

Management of non-compressible torso hemorrhage: An update.

With the widespread adoption of advanced tourniquets, the mortality rate of limb wound hemorrhage has decreased significantly, and non-compressible torso hemorrhage has gradually occupied the leading position of potentially preventable death, both in military and civilian circumstances. With the emergence of novel hemostatic devices and materials, strategies for the management of non-compressible torso hemorrhage have changed significantly. This review summarizes the current treatment strategies and types of equipment for non-compressible torso hemorrhage and suggests future research directions, hoping to provide a comprehensive review for the medical personnel and researchers engaging in this field.

Candidal periprosthetic joint infection after primary total knee arthroplasty combined with ipsilateral intertrochanteric fracture: A case report.

BACKGROUND: Candidal periprosthetic joint infection is a rare and difficult to diagnose complication of total knee arthroplasty. The treatment of such complications is inconclusive and may include prosthesis removal, debridement, arthrodesis, and extensive antifungal therapy to control the infection. CASE SUMMARY: A 62-year-old male with a history of total knee arthroplasty (TKA) in his left knee presented with ipsilateral knee pain and a sinus discharge 20 mo after TKA. The patient was previously evaluated for left knee pain, swelling, and a transient fever one month postoperatively. Prothesis removal and insertion of a cement spacer were performed in a local hospital six months prior to the current presentation. Medical therapy included rifampicin and amphotericin which were administered for 4 wk following prosthesis removal. A second debridement was performed in our hospital and Candida parapsilosis was detected in the knee joint. Fourteen weeks following the latter debridement, the patient suffered a left intertrochanteric fracture and received closed reduction and internal fixation with proximal femoral nail anterotation. Two weeks after fracture surgery, a knee arthrodesis with autograft was performed using a double-plate fixation. The patient recovered adequately and was subsequently discharged. At the two-year follow-up, the patient has a stable gait with a pain-free, fused knee. CONCLUSION: Fungal periprosthetic joint infection following TKA may be successfully and safely treated with prosthesis removal, exhaustive debridement, and arthrodesis after effective antifungal therapy. Ipsilateral intertrochanteric fractures of the affected knee can be safely fixated with internal fixation if the existing infection is clinically excluded and aided by the investigation of serum inflammatory markers.

Relationship between bovine oocytes developmental competence and mRNA expression of apoptotic and mitochondrial genes following the change of vitrification temperatures and cryoprotectant concentrations.

The present study analyzed the relationship between bovine oocytes developmental competence and mRNA expression of apoptotic and mitochondrial genes following the change of vitrification temperatures (VTs) and cryoprotectant agent concentrations (CPAs). Cumulus oocyte complexes were randomly divided into five groups: control, vitrified in liquid nitrogen (LN; -196 °C) with 5.6 M CPAs (LN 5.6 M), LN with 6.6 M CPAs (LN 6.6 M), liquid helium (LHe; -269 °C) with 5.6 M CPAs (LHe 5.6 M), and LHe with 6.6 M CPAs (LHe 6.6 M). After vitrification and warming, oocytes of vitrified and control groups were subjected to in vitro maturation (IVM), in vitro fertilization and in vitro culture. The blastocyst rate in LHe 5.6 M group was the highest among the four vitrified groups (13.7% vs. 9.4%, 1.3%, and 8.4%; P < 0.05). The mRNA expression level of 8 apoptotic- and 12 mitochondria-related genes were detected through qRT-PCR after IVM. Lower VT (LHe, -269 °C) positively affected the mRNA expression levels of apoptotic genes (BAD, BID, BTK, TP53, and TP53I3) and mitochondrial genes (COX6B1, DERA, FIS1, NDUFA1, NDUFA4, PRDX2, SLC25A5, TFB1M, and UQCRB), and reduced oxidative stress from freezing. Decreased CPAs (5.6 M) positively affected mRNA expression levels of apoptotic genes (BAD, BCL2A1, BID, and CASP3) in LHe vitrification but negatively affected apoptotic genes (BAD, BAX, BID, BTK, and BCL2A1) in LN vitrification. In conclusion, decreased VTs and CPAs in LHe vitrification may increase the blastocyst rate by changing the mRNA expression levels of these apoptotic and mitochondrial genes for the vitrified oocytes.

Effect of HBx on inflammation and mitochondrial oxidative stress in mouse hepatocytes.

Hepatitis B virus × protein (HBx) serves an important role in the pathogenesis of the hepatitis B virus infection. Previous studies have reported that the interaction between HBx and hepatocyte mitochondria is an important factor leading to liver cell injury and apoptosis, ultimately inducing the formation of liver cancer. In the present study, a mouse model expressing HBx was constructed using hydrodynamic in vivo transfection based on the interaction between HBx and cytochrome c oxidase (COX) subunit III. The specific mechanism of HBx-induced oxidative stress in mouse hepatocytes and the subsequent effect on mitochondrial function and inflammatory injury was assessed. The results demonstrated that HBx reduced the activity of COX and the expression of superoxide dismutase and upregulated the expression of malondialdehyde, NF-κB and phospho-AKT, thus increasing oxidative stress. In addition, HBx induced an increase in interleukin (IL)-6, IL-1ß and IL-18 expression levels, which created an inflammatory microenvironment in the liver, further promoting hepatocyte inflammatory injury. Therefore, it was proposed that HBx may affect hepatocyte mitochondrial respiration by reducing the activity of cytochrome c oxidase, leading to mitochondrial dysfunction and inducing hepatocyte inflammation and injury.

Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents.

A novel series of graveolinine derivatives were synthesized and evaluated as potential anti-Alzheimer agents. Compound 5f exhibited the best inhibitory activity for acetylcholinesterase (AChE) and had surprisingly potent inhibitory activity for butyrylcholinesterase (BuChE), with IC50 values of 0.72 µM and 0.16 µM, respectively. The results from Lineweaver-Burk plot and molecular modeling study indicated non-competitive inhibition of AChE by compound 5f. In addition, these derivatives showed potent self-induced ß-amyloid (Aß) aggregation inhibition. Moreover, 5f didn't show obvious toxicity against PC12 and HepG2 cells at 50 µM. Finally, in vivo studies confirmed that 5f significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, these graveolinine derivatives should be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Effect of vitrification temperature and cryoprotectant concentrations on the mRNA transcriptome of bovine mature oocytes after vitrifying at immature stage.

The present study aimed to investigate the effect of vitrification temperature (VT) and cryoprotective agent concentrations (CPAs) on the mRNA transcriptome of bovine mature oocytes after vitrifying at immature stage. Cumulus oocyte complexes (COCs) were randomly divided into the following five groups: fresh oocytes (control), oocytes vitrified in liquid helium (LHe; -269 °C) with 5.6 M CPAs (LHe 5.6 M), oocytes vitrified in LHe with 6.6 M CPAs (LHe 6.6 M), oocytes vitrified in liquid nitrogen (LN; -196 °C) with 5.6 M CPAs (LN 5.6 M), and oocytes vitrified in LN with 6.6 M CPAs (LN 6.6 M). We performed two experiments in this study. In experiment 1, after vitrification and thawing, oocytes of vitrified and control groups were subjected to in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC). The rates of normal morphology, maturation, cleavage, and blastocyst formation in LHe 5.6 M were higher than those in LN 5.6 M (P < 0.05). The rates of normal morphology and cleavage in LHe 6.6 M were higher than those in LN 6.6 M (P < 0.05). However, the maturation and blastocyst rates were similar (P > 0.05) between LHe 6.6 M and LN 6.6 M. The blastocyst rate of 13.31% in LHe 5.6 M was the highest among all vitrified groups (P < 0.05). In experiment 2, the mRNA transcriptome of each sample was analyzed by Smart-Seq4, and the differentially expressed genes (DEGs) were detected by edgeR (P ≤ 0.05; fold-change ≥ 2). A total of 505 DEGs (342 upregulated and 163 downregulated genes) were detected in LHe 5.6 M; 609 DEGs (493 upregulated and 116 downregulated genes) were detected in LHe 6.6 M; 218 DEGs (101 upregulated and 117 downregulated genes) were determined in LN 5.6 M; and 221 DEGs (104 upregulated and 117 downregulated genes) were detected in LN 6.6 M. LHe vitrification affected the mRNA transcriptome of bovine mature oocytes after vitrifying at immature stage mainly by upregulating gene expression. Decreased CPAs (5.6 M) reduced the effect of vitrification on mRNA transcriptome when LHe vitrification was used. Among the DEGs closely related to bovine oocytes, the genes possibly related to VT were ND2, MPV17L2, PIF1, LPIN1, IMP3, BRD1, DCTN3, DERA, ATP7B, NEK5, HVCN1, and MARK2. The gene that may be associated with CPAs is CC2D2A. Genes that may be affected by VT and CPAs included PGK1, SLC7A3, FITM2, NPM3, ISCU, CWC15, and PSAP.

The application of 595-nm pulsed dye laser for vascular anomalies in a Chinese population: a 10-year experience.

BACKGROUND: The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques. OBJECTIVE: To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients. METHOD: We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment. RESULTS: Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p < 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p < 0.05). There was no significant correlation between efficacy and age or sex (p > 0.05). CONCLUSION: PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results.  Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.

Rhynchophylline suppresses soluble Aß1-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors.

Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid ß protein (Aß) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aß-induced neurotoxicity. However, whether RIN can prevent soluble Aß1-42-induced impairments in spatial cognitive function and synaptic plasticity is still unclear. Using the combined methods of behavioral tests, immunofluorescence and electrophysiological recordings, we characterized the key neuroprotective properties of RIN and its possible cellular and molecular mechanisms against soluble Aß1-42-related impairments in rats. Our findings are as follows: (1) RIN efficiently rescued the soluble Aß1-42-induced spatial learning and memory deficits in the Morris water maze test and prevented soluble Aß1-42-induced suppression in long term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) circuit. (2) Excessive activation of extrasynaptic GluN2B-NMDAR and subsequent Ca2+ overload contributed to the soluble Aß1-42-induced impairments in spatial cognitive function and synaptic plasticity. (3) RIN prevented Aß1-42-induced excessive activation of extrasynaptic NMDARs by reducing extrasynaptic NMDARs -mediated excitatory postsynaptic currents and down regulating GluN2B-NMDAR expression in the DG region, which inhibited Aß1-42-induced Ca2+ overload mediated by extrasynanptic NMDARs. The results suggest that RIN could be an effective therapeutic candidate for cognitive impairment in AD.

Analysis of missed diagnosis of orbital foreign bodies.

A clinical analysis of diagnosis was performed as well as the management of orbital foreign bodies, to investigate the methods to avoid missed diagnosis. A total of 15 cases of an orbital foreign body was reviewed, and for these cases, the clinical manifestation, imaging data and operative situation were studied. Among the patients, 4 cases turned out to have wooden, 3 metallic, 2 glass, 2 bones, and 4 other foreign bodies. Twelve cases had received debridement and suture before our management, and 1 foreign body was treated more than once. In conclusion, detailed traumatic history and imaging examination are necessary for the diagnosis of orbital foreign bodies, while prompt diagnosis, accurate location and professional surgical skills are important for the treatment.

Lung ultrasound for the diagnosis of pneumonia in adults: A meta-analysis.

BACKGROUND: Pneumonia is a common and serious infectious disease that can cause high mortality. The role of lung ultrasound (LUS) in the diagnosis of pneumonia is becoming more and more important. METHODS: In the present study, we collected existing evidence regarding the use of LUS to diagnose pneumonia in adults and conducted a systematic review to summarize the technique's diagnostic accuracy. We specifically searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase databases and retrieved outcome data to evaluate the efficacy of LUS for the diagnosis of pneumonia compared with chest radiography or chest computed tomography. The pooled sensitivity (SEN) and specificity (SPE) were determined using the Mantel-Haenszel method, and the pooled diagnostic odds ratio (DOR) was determined using the DerSimonian-Laird method. We also assessed heterogeneity of sensitivity, specificity, and diagnostic odds ratio using the Q and I statistics. RESULTS: Twelve studies containing 1515 subjects were included in our meta-analysis. The SEN and SPE were 0.88 (95% CI: 0.86-0.90) and 0.86 (95% CI: 0.83-0.88), respectively. The pooled negative likelihood ratio (LR) was 0.13 (95% CI: 0.08-0.23), the positive LR was 5.37 (95% CI: 2.76-10.43), and the DOR was 65.46 (95% CI: 29.24-146.56). The summary receiver operating characteristic curve indicated a relationship between sensitivity and specificity. The area under the curve for LUS was 0.95. CONCLUSION: LUS can help to diagnose adult pneumonia with high accuracy.

Lysosomal ATP imaging in living cells by a water-soluble cationic polythiophene derivative.

Lysosomes in astrocytes and microglia can release ATP as the signaling molecule for the cells through ca(2+)-dependent exocytosis in response to various stimuli. At present, fluorescent probes that can detect ATP in lysosomes have not been reported. In this work, we have developed a new water-soluble cationic polythiophene derivative that can be specifically localized in lysosomes and can be utilized as a fluorescent probe to sense ATP in cells. PEMTEI exhibits high selectivity and sensitivity to ATP at physiological pH values and the detection limit of ATP is as low as 10(-11)M. The probe has low cytotoxicity, good permeability and high photostability in living cells and has been applied successfully to real-time monitoring of the change in concentrations of ATP in lysosomes though fluorescence microscopy. We also demonstrated that lysosomes in Hela cells can release ATP through Ca(2+)-dependent exocytosis in response to drug stimuli.

[Clinical and echocardiographic features of cardiac myxomas in 64 patients].

OBJECTIVE: To summarize the clinical and echocardiographic features of cardiac myxomas. METHODS: The medical records of patients with diagnosis of cardiac myxomas who hospitalized in our department from October 1985 to February 2011 were analyzed. RESULTS: A total of 64 patients were enrolled [40 female, the mean age was 2 - 77 (47 ± 17) years]. The main complaints were palpitation (n = 24, 38%), short breath (n = 23, 36%), fever (n = 13, 20%), chest tightness (n = 11, 17%), dizziness (n = 10, 16%), fatigue (n = 10, 16%), weight loss (n = 10, 16%), syncope (n = 9, 14%), edema (n = 8, 13%); and thrombus embolisms (n = 13, 20%), including stroke (n = 7, 11%) and periphery artery embolism (n = 6, 9%). The interval from symptoms onset to diagnosis (surgical removal) ranged from 1 day to 9 years (median: 3 months). Single myxoma was detected in 62 (97%) patients (58 in left atria, 2 in right atria and 2 in right ventricle) and multiple myxomas were found in 2 (3%) patients and one patient was diagnosed as Carney syndrome. The mean size of tumor assessed by echocardiography was (5.0 ± 1.8) cm × (2.9 ± 1.0) cm. All myxomas were surgically removed (54 patients received operation in our hospital and 10 patients were operated in other hospitals) and diagnosis was confirmed during operation and the mean myxoma size obtained from operation was (5.4 ± 1.6) cm × (3.6 ± 1.3) cm × (2.6 ± 1.2) cm (P > 0.05 vs. tumor size assessed by echocardiography). The locations of tumor stalks found by echocardiography were confirmed during surgery in most cases (97%). Incidence of NYHA class III diagnosis was more often in patients with right heart myxomas [3 cases (3/4)] than in patients with left atrium myxomas [17% (10/58), P < 0.05]. CONCLUSIONS: Clinical manifestations of cardiac myxomas were various and non-specific. Echocardiography remains the most valuable diagnosis tool for patients with cardiac myxomas.