Ag(I)-Mediated Annulation of 2-(2-Enynyl)pyridines and Propargyl Amines to Access 1-(2H-Pyrrol-3-yl)indolizines.

An effective Ag(I)-mediated annulation of 2-(2-enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2H-pyrrol-3-yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2H-pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Base-Promoted Decarboxylative Annulation of Methyl 2-(2-Bromophenyl)acetates and Ynones to Access Benzoxepines.

A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates has been developed. A broad range of benzoxepines were prepared with a broad substrate scope and high regioselectivity in moderate to excellent yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and the intramolecular nucleophilic aromatic substitution reaction. Additionally, the key intermediates were successfully obtained and characterized unambiguously by single-crystal X-ray crystallography, which could favorably support a decarboxylative annulation mechanism. Furthermore, gram-scale reaction and synthetic applications for the further functionalization are also studied.

Base-Promoted Divergent Annulation of Conjugated Ynones and Methyl 2-(Cyanomethyl)benzoates to Access 1-Naphthols and Xanthones.

A facile and efficient base-mediated divergent annulation of methyl 2-(cyanomethyl)benzoates and conjugated ynones has been described. A broad range of 1-naphthols and xanthones were formed in moderate to excellent yields. The notable features of this protocol include readily available precursors, broad substrate scope, complete regioselectivity, and substrate-controlled divergent synthesis. The gram-scale preparation and synthetic transformations of the resulting 1-naphthols and xanthones demonstrate their utility.

Transition-Metal-Free Synthesis of 3-Acyl Chromones by the Tandem Reaction of Ynones and Methyl Salicylates.

A facile and effective tandem reaction of ynones and methyl salicylates was developed to obtain a broad range of 3-acyl chromones in moderate-to-excellent yields. This protocol underwent a Michael addition and cyclization process, which exhibited easily accessible substrates, broad substrate scope, and high regioselectivity under mild and transition-metal-free conditions. Moreover, gram-scale reaction and further chemical transformation of the products were also further studied.

Reduction in Allergenicity and Induction of Oral Tolerance of Glycated Tropomyosin from Crab.

Tropomyosin (TM) is an important crustacean (Scylla paramamosain) allergen. This study aimed to assess Maillard-reacted TM (TM-G) induction of allergenic responses with cell and mouse models. We analyzed the difference of sensitization and the ability to induce immune tolerance between TM and TM-G by in vitro and in vivo models, then we compared the relationship between glycation sites of TM-G and epitopes of TM. In the in vitro assay, we discovered that the sensitization of TM-G was lower than TM, and the ability to stimulate mast cell degranulation decreased from 55.07 ± 4.23% to 27.86 ± 3.21%. In the serum of sensitized Balb/c mice, the level of specific IgE produced by TM-G sensitized mice was significantly lower than TM, and the levels of interleukins 4 and interleukins 13 produced by Th2 cells in spleen lymphocytes decreased by 82.35 ± 5.88% and 83.64 ± 9.09%, respectively. In the oral tolerance model, the ratio of Th2/Th1 decreased from 4.05 ± 0.38 to 1.69 ± 0.19. Maillard reaction masked the B cell epitopes of TM and retained some T cell epitopes. Potentially, Maillard reaction products (MRPs) can be used as tolerance inducers for allergen-specific immunotherapy.

[Analysis of the Importance of Incorporating Legal Education in Medical Education in the Context of the New Medicine Strategy].

In line with the Healthy China strategy, new requirements for medical education have been raised. Medical education against the background of a new model of medicine demands an effective response to its inherent complex elements concerning the rule of law. During the course of the implementation of the new medicine strategy, in face of the widening scope of medical risks, the growing awareness of patient rights, and the conventional logic of medical education, elements concerning the rule of law should be incorporated in medical education in the early stage so as to help medical practitioners develop the appropriate legal literacy and rely on ideas of rules, equality and ethical bottomlines to analyze and solve problems. Thus, medical practitioners would be better equiped to effectively respond to the legal problems they encounter in their medical practice. Legal education is the route of choice in response to the transformation in the mode of medical education and the attempt to solve complicated problems through medicine and the rule of law. Through legal education, the risks of technology embeddedness could be avoided, the relationship between patients and medical practitioners could be regulated in a standardized way, and the medical humanistic environment could be reshaped, thereby improving the quality and level of new medical education.

Degraded polysaccharides from Porphyra haitanensis: purification, physico-chemical properties, antioxidant and immunomodulatory activities.

To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of → 3) ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →, and → 3) ß-D-galactose (1 → 4) α-L-galactose-6-S (1 →, and → 3) 6-O-methyl-ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.

Phosphine-Catalyzed Synthesis of 3-Allyl-4-pyrones by the Tandem Reaction of Diynones and Allylic Alcohols.

A simple and effective tandem reaction of diynones and allylic alcohols was developed to afford functionalized 3-allyl-4-pyrones in moderate to excellent yields. This protocol underwent a Michael addition─Claisen rearrangement─O-cyclization process, which exhibited broad substrate tolerance, high regioselectivity, and atom economy under a metal-free condition. Moreover, functional transformation of the products was also further studied.

Catalyst- and Additive-Free Annulation of Ynediones and (Iso)Quinoline N-Oxides: An Approach to Synthesis of Pyrrolo[2,1-a]Isoquinolines and Pyrrolo[1,2-a]Quinolines.

A simple and effective annulation of ynediones and (iso)quinoline N-oxides was developed to afford various functionalized pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines in moderate to excellent yields. This protocol underwent a tandem [3 + 2] cycloaddition/ring-opening/N-nucleophilic addition, which exhibited high regioselectivity, broad substrate tolerance, and atom economy under catalyst-, additive-free, and air conditions. Moreover, indolizine was also successfully prepared using pyridine N-oxide.

Histamine H1 Receptor Contributes to Vestibular Compensation.

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.

Synthesis of 1-Cyano-3-acylnaphthalenes via Formal [4+2] Benzannulation of 2-(2-Alkynylphenyl)acetonitriles and Alkynones.

Effective transition-metal-free formal [4+2] benzannulation for the preparation of 1-cyano-3-acylnaphthalenes from 2-(2-alkynylphenyl)acetonitriles and alkynones through sequential C-C bond coupling has been developed. This protocol is characterized by mild conditions, excellent functional group tolerance, complete regioselectivity, and atom economy. The plausible mechanism, gram-scale synthesis, and further transformations of the product were studied.

An efficient tandem synthesis of chromones from o-bromoaryl ynones and benzaldehyde oxime.

An effective transition-metal-free strategy was developed for the preparation of chromones from o-bromoaryl ynones and benzaldehyde oxime through sequential C-O bond formation. This cyclization reaction could well tolerate a wide range of functional groups, and the corresponding chromones were given in moderate to excellent yields. Mechanistically, benzaldehyde oxime as a hydroxide source and 1,3-diketone derivatives as reaction intermediates were involved in this transformation.

An efficient preparation of ß-ketophosphine oxides from alkynylphosphine oxides with benzaldehyde oxime as a hydroxide source.

An effective and facile transition-metal-free method has been developed for the synthesis of ß-ketophosphine oxides from alkynylphosphine oxides with benzaldehyde oxime as a hydroxide surrogate. The current methodology provides simple access to various ß-ketophosphine oxides in moderate to excellent yields with a broad substrate scope.

Effects of Levosimendan on Right Ventricular Function in Patients with Acute Decompensated Heart Failure.

BACKGROUND: To investigate the effects of levosimendan on right ventricular (RV) function in patients with acute decompensated heart failure (ADHF). METHODS: Patients with ADHF admitted from January 2017 to October 2017 were enrolled in this study. The patients were randomized to receive 24-h intravenous levosimendan or placebo. Echocardiographic examinations were performed and the parameters were compared. Epidemiological data were recorded and compared before and after treatment. Major adverse cardiac events during hospitalization and during 1-month follow-up were compared. RESULTS: The baseline characteristics were comparable. After 24-h infusion of levosimendan and placebo, the left ventricular ejection fraction and S' were significantly increased in the levosimendan group compared with the control group (both p < 0.05). The E value in the levosimendan group significantly decreased (75.38 ± 8.32 vs. 88.21 ± 10.36, p < 0.0001), and E/e' significantly increased in the control group (19.61 ± 6.52 vs. 27.58 ± 8.22, p < 0.0001). The levels of right ventricular fractional area change (24 ± 3 vs. 20 ± 2, p < 0.0001) and tricuspid annular plane systolic excursion (1.56 ± 0.36 vs. 1.38 ± 0.21, p < 0.0001) were significantly higher in the levosimendan group than in the control group. After treatment, the values of systolic pulmonary artery pressure (SPAP) decreased in both groups (both p < 0.05), and the value of SPAP in the levosimendan group was lower than that in the control group (47.22 ± 5.6 vs. 55.85 ± 7.41, p < 0.0001). After 1-month follow-up, there was no significance in readmissions due to recurrent heart failure. CONCLUSIONS: Levosimendan seems to provide more beneficial effects among patients with ADHF to improve RV function, along with a decrease in pulmonary pressure.

An effective preparation of both 1,3-diketones and nitriles from alkynones with oximes as hydroxide sources.

An effective phosphine-catalyzed protocol has been established for the syntheses of 1,3-diketones and nitriles from alkynones with oximes as hydroxide surrogates. This method features the use of a phosphine catalyst, compatibility with various functional groups and ambient temperature, which makes this approach very practical. A plausible mechanism was proposed.

Efficacies of Various Surgical Regimens in the Treatment of Renal Calculi Patients: a Network Meta-Analysis in 25 Enrolled Controlled Clinical Trials.

BACKGROUND/AIMS: Renal calculi, or kidney stones, are masses made of crystals that affect people of all geographical, cultural, and racial groups. We conduct this study with the aim of comparing the efficacy of various surgical methods in the treatment of renal calculi. METHODS: Controlled clinical trials (CCTs) related to different surgical treatment approaches for renal calculi were included in this study by retrieving them from electronic English databases. The odds ratios (OR), the weighted mean difference (WMD), 95% confidence intervals (95% CI) and surface under the cumulative ranking curves (SUCRA) were evaluated, followed by a cluster analysis. RESULTS: Compared with the extracorporeal shockwave lithotripsy (SWL), minimally invasive percutaneous nephrolithotomy (mini-PCNL), retrograde intrarenal surgery (RIRS), standard percutaneous nephrolithotomy (standard PCNL), ureterorenoscopy (URS) and micro-percutaneous nephrolithotomy (microperc) regimens, the open anatrophic nephrolithotomy (Open AN), URS + RIRS and laparoscopic pyelolithotomy (LP) surgical procedures all presented with a higher stone-free rate in renal calculi. Lower auxiliary procedures were found in the URS + RIRS treatment approach compared with SWL, RIRS, URS and microperc regimens. In addition, the SWL regimen indicated a lower stone-free rate than the mini-PCNL, standard PCNL, Open AN, URS + RIRS and LP regimens. Finally, the RIRS regimen presented with the shortest in-patient stay compared to the mini-PCNL, standard PCNL, Open AN, URS, URS + RIRS and LP regimens. CONCLUSION: This meta-analysis demonstrated that the URS + RIRS surgical procedure has the best stone-free rate and the lowest number of auxiliary procedures. The RIRS and Microperc both have the shortest hospital stay and operative time.

The Wilms tumor gene, Wt1, is critical for mouse spermatogenesis via regulation of sertoli cell polarity and is associated with non-obstructive azoospermia in humans.

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.

Surgical treatment of gynecomastia: mastectomy compared to liposuction technique.

BACKGROUND: Gynecomastia is a benign enlargement of the male breast. Yet enlarged breasts cause anxiety, embarrassment, psychosocial discomfort, and fear of breast cancer. The aim of this study was to assess the experience of gynecomastia patients undergoing mastectomy and liposuction surgery. METHODS: Seven hundred thirty-three patients were analyzed for age, chief complaint, position, grade, operation approach, biopsy, and complication between mastectomy group and liposuction group, from 1990 to 2010. RESULTS: Four hundred two patients (436 breasts) were treated with mastectomy and 331 patients (386 breasts) were treated with liposuction techniques. Three hundred thirty (82%) patients complained of breast lump and lump with pain in mastectomy group, and 204 (61%) patients complained of enlargement breast and enlargement with pain in liposuction group (P < 0.05). All excision specimens were performed for routine histological analysis which showed pathologic diagnosis in patients with mastectomy (100%). One hundred fifty-nine (41%) patients with liposuction acquired pathologic diagnosis through fine needle aspiration and/or core biopsy (P < 0.05). The reoperation rates in mastectomy group and liposuction group were 1.4% and 0.5%, respectively. There were no nipple/areola necrosis and scars in liposuction group. CONCLUSIONS: The surgical treatment of gynecomastia required an individual approach, depending on symptoms (lump or enlargement) and requirements of patients. Patients who chose mastectomy were looking for reassurance that their pathologic diagnosis was benign. The increase in the number of liposuction patients was reflected in our study because it was associated with superior esthetic results and few complications.

Thrombolysis Followed by Early Percutaneous Coronary Intervention via Transradial Artery Approach in Patients with ST-Segment Elevation Infarction.

BACKGROUND: The purpose of this study was to investigate the safety and efficacy of thrombolysis followed by early percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 161 patients were enrolled in the study. Fifty-three of them who underwent thrombolysis in non-PCI hospital and immediately transferred to receive early PCI were assigned to the early PCI group (E-PCI); the rest of the patients were assigned to the primary PCI group (P-PCI). Coronary angiography and PCI were performed via the transradial artery approach for patients in both groups. Angiographic parameters, bleeding complications and total hospital stay were compared between the two groups. All patients were followed-up for 30 days to evaluate major adverse cardiac events (MACE). RESULTS: Before PCI procedure, the thrombus score of IRA in the E-PCI group was lower, and the percentage of TIMI flow grade (TFG) 3 was higher (both p < 0.05) compared to those in the P-PCI group. The myocardial reperfusion in the E-PCI group was better than that in the P-PCI group. There was a trend towards a lower peak value of serum creatine kinase MB in the E-PCI group, and left ventricular ejection fraction (LVEF) before discharge in E-PCI was higher than that in the P-PCI group (54.38 ± 5.29% vs. 52.19 ± 7.00%, respectively, p = 0.028). No significant differences were found in the incidences of bleeding complications and hospital stay between the two groups. There was no significant difference in the 30-day MACE between the two groups (p = 0.863), and no significance of cumulative MACE-free survival rates were found between the two groups as well (p = 0.522). Variables predicting MACE upon patient follow-up according to univariable Cox regression analyses showed that a history of hyperlipidemia, smokers, TFG of infarction related artery before PCI < 2, and low levels of LVEF were associated with poor clinical outcomes (all p < 0.05). CONCLUSIONS: It is safe and efficacious for STEMI patients to receive thrombolysis followed by early PCI via the transradial artery approach. KEY WORDS: Major adverse cardiac event; Percutaneous coronary intervention; Radial artery; ST-segment elevation myocardial infarction; Thrombolysis.