Access to 2-Alkyltropones via Organic Base-Catalyzed Tandem Deamination and Aldol Condensation of Tropinone-Derived Quaternary Ammonium Salts.

The tropone skeleton exists in a number of natural products and bioactive substances, and currently, the applications of substituted tropones are significantly limited by their preparative methods. Herein, we report a very convenient method to access 2-alkyltropones via organic base-catalyzed tandem reaction of tropinone-derived quaternary ammonium salts. Tropinone methiodide reacted with a wide variety of aromatic and aliphatic aldehydes in the presence of 1,4-diazabicyclo[2.2.2]octane to afford structurally diverse 2-alkyltropones in moderate to excellent yields with extremely high site selectivity. The reaction employs readily available feedstocks and reagents, is free of transition metals and compatible with water and air, tolerates a variety of functional groups, and can be easily scaled up. Moreover, the products are amenable to various synthetic transformations. Preliminary mechanistic studies revealed that the reaction proceeded via tandem deamination, aldol condensation, and isomerization.

Sound transmission across locally resonant honeycomb sandwich meta-structures with large spatial periodicity.

Honeycomb sandwich structures have been widely used in the field of engineering owing to their outstanding mechanical properties. However, for a honeycomb sandwich structure with large spatial periodicity, there is a low-frequency sound insulation valley. Here, the sound transmission across locally resonant honeycomb sandwich meta-structures was investigated to overcome this sound-insulation valley. An analytical model was developed based on the space-harmonic approach and the low-frequency sound insulation valley was determined analytically and numerically. The results indicate that the resonator distributed at the center of the face panel has a significant impact on the sound transmission performance of the honeycomb sandwich structure, whereas the resonator distributed on the wall of the honeycomb core does not contribute to overcoming this sound-insulation valley. Based on the research results, a design strategy for overcoming this sound-insulation valley was determined by tuning the damping parameter and constructing graded resonators. Moreover, sound transmission under the excitation of oblique incidence sound waves was also investigated. Compared with the method of filling porous materials, the proposed design method is more effective, and more importantly, the mass of the resonator is only 1.23% of that of the porous materials.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Visual Dysfunction is a Risk Factor of Postoperation Delirium in Parkinson Disease.

OBJECTIVE: To investigate the incidence of and factors influencing postoperative delirium (POD) in Parkinson disease after deep brain stimulation (DBS) surgery. METHODS: A total of 272 patients with Parkinson disease who underwent DBS completed the Visual Impairment in Parkinson Disease Questionnaire (VIPD-Q) and underwent neuro-ophthalmologic examinations including optical coherence tomography and fundus vessel analysis. We retrospect the prevalence of POD in groups with different VIPD-Q scores, retinal nerve fiber layer (RNFL) thicknesses, and vessel percentage areas (VPA). A predictive model based on the VIPD-Q was constructed using multivariate logistic regression and verified using bootstrap validation. RESULTS: POD was experienced by 65 (23.9%) of 272 patients. Patients with PD who had visual impairment (VIPD-Q > 6) had a higher incidence of POD (chi-square, P < 0.001). The thickness of the RNFL and VPA were also correlated with POD risk. Differences in implantation locations (subthalamic nucleus or pars interna of globus pallidus), operation times, and general anesthesia times did not affect the prevalence of DBS-related POD. A nomogram was constructed based on ophthalmic events to predict the risk of POD. CONCLUSIONS: The study findings provide convincing evidence of the relationship between visual dysfunction and the risk of POD. In view of the higher risk of POD, visually impaired patients with PD should undergo closer monitoring after DBS surgery.

Synthesis and Antibacterial Activity of Spiro[4H-pyran-3,3'-oxindoles] Catalyzed by Tröger's Base Derivative.

OBJECTIVE: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared via the one pot reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins and malononitrile successfully catalyzed by a Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]-1,5-diazadicyclo[3.3.1]-2,6-octadiene). The antibacterial activity of products against three wild-type bacteria (B. subtilis, S. aureus, and E. coli) and two resistant strains (Methicillin-resistant S. aureus (18H8) and E. coli carrying the BlaNDM-1 gene (18H5)) was evaluated using the minimum inhibitory concentration (MIC).. METHODS: 1-Phenyl-1,3-butanedione 2 or dibenzoylmethane 2' (0.42 mmol), substituted isatin 3 (0.4 mmol), malononitrile 4 (0.8 mmol), Tröger's base derivative 1b (0.08 mmol), and 10 mL of acetonitrile were added to a 50 mL round bottom flask and refluxed. After the completion (TLC monitoring), water (10 mL) was added to the reaction mixture; pH = 7 was adjusted with saturated NaHCO3 (aq.), and the mixture was extracted with CH2Cl2 (50 mL × 3). Organic layers were combined and dried with anhydrous Na2SO4; the solvent was removed under vacuum, and the residue was purified by column chromatography (VDCM: VMeOH = 80: 1) to afford product 5. The antibacterial activity was tested by the MTT method. RESULTS: Seventeen spiro[4H-pyran-3,3'-oxindole] derivatives were synthesized through the reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot in medium to high yields. Four compounds showed antibacterial activity, and two of them showed the same activity as the positive control Ceftazidime on S. aureus (MIC = 12.5 µg/mL). CONCLUSION: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared, and their antibacterial activity was evaluated. Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]- 1,5-diazadicyclo[3,3,1]-2,6-octadiene) was used as an efficient organocatalyst for the reaction of low reactive chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot successfully and effectively by providing multiple active sites and alkaline environment. By the theoretical calculation, we explained the possible reaction sequence and mechanism. Due to the superiority and high efficiency of the TB framework as an organocatalyst, the reaction showed many advantages, including mild reaction conditions, low catalyst loading, and a wide substrate range. It expanded the application of Tröger's base to the multicomponent reaction in organocatalysis. Some products were screened due to their high antibacterial activity in vitro, showing their potential in new antibacterial drug development.

Ophthalmologic problems correlates with cognitive impairment in patients with Parkinson's disease.

Objective: Visual impairment is a common non-motor symptom (NMS) in patients with Parkinson's disease (PD) and its implications for cognitive impairment remain controversial. We wished to survey the prevalence of visual impairment in Chinese Parkinson's patients based on the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q), identify the pathogens that lead to visual impairment, and develop a predictive model for cognitive impairment risk in Parkinson's based on ophthalmic parameters. Methods: A total of 205 patients with Parkinson's disease and 200 age-matched controls completed the VIPD-Q and underwent neuro-ophthalmologic examinations, including ocular fundus photography and optical coherence tomography. We conducted nomogram analysis and the predictive model was summarized using the multivariate logistic and LASSO regression and verified via bootstrap validation. Results: One or more ophthalmologic symptoms were present in 57% of patients with Parkinson's disease, compared with 14% of the controls (χ2-test; p < 0.001). The visual impairment questionnaire showed good sensitivity and specificity (area under the curve [AUC] = 0.918, p < 0.001) and a strong correlation with MoCA scores (Pearson r = -0.4652, p < 0.001). Comparing visual impairment scores between pre- and post-deep brain stimulation groups showed that DBS improved visual function (U-test, p < 0.001). The thickness of the retinal nerve fiber layer and vessel percentage area predicted cognitive impairment in PD. Interpretation: The study findings provide novel mechanistic insights into visual impairment and cognitive decline in Parkinson's disease. The results inform an effective tool for predicting cognitive deterioration in Parkinson's based on ophthalmic parameters.

Comprehensive assessment of the ecological risk of exposure to triphenyl phosphate in a bioindicator tadpole.

The toxicity of triphenyl phosphate (TPhP) to aquatic organisms in surface waters has been demonstrated; However, an understanding of toxicity profiles of TPhP in amphibians is limited. Therefore, the adverse effects and threshold concentrations of TPhP on metamorphosis, growth, locomotion, and hepatic antioxidants of Gosner stage 25 Polypedates megacephalus tadpoles under long-term (35 d) exposure to six TPhP concentrations until complete metamorphosis were assessed. Additionally, the overall effect of using integrated multiple biomarkers were determined to demonstrate the potential ecological risks of waterborne TPhP at environmentally relevant concentrations in amphibian tadpoles. With increasing TPhP concentrations, physical parameters (snout-vent length, body mass, condition factor, and hepatic somatic index), jumping distance, hepatic catalase, and superoxide dismutase activities decreased, whereas metamorphosis time and malondialdehyde content increased. The threshold concentration of TPhP that affected the tadpole biomarker, except for metamorphosis rate and jumping distance, was 50-400 µg/L. Furthermore, the standardized scores of the examined integrated biomarkers in the six TPhP concentrations were visualized using radar plots and calculated as the integrated biomarker responses (IBRs). The varying TPhP concentrations had different scores in the radar plots, and the threshold for affecting the IBR value was 10 µg/L, which was close to the TPhP concentration in surface waters. Additionally, IBR values were strongly positively correlated with the TPhP concentrations. These findings indicate that environmentally relevant exposure to waterborne TPhP can pose an ecological risk to amphibian tadpoles. This study can serve as a reference and assist in the formulation of relevant policies and strategies to control TPhP pollution in water bodies.

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients.

Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.

[Distribution, Sources, and Risk Assessment of Polyfluoroalkyl Substances in Main Rivers and Soils of Tianjin].

Rapid urbanization and industrialization may potentially impact the spatial distribution and transmission of polyfluoroalkyl substances (PFASs). Tianjin, a typical industrialized city with a high urbanization level around Bohai Bay, was selected to evaluate the spatial distribution and ecological risks of PFASs. Water and soil samples were systematically collected and analyzed by using solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) methods. The results showed that all 12 PFASs were detected in water and soils, and the detection rates of the other congeners were low. The concentrations of ΣPFASs in water ranged from 3.93 to 357.85 ng ·L-1, and the levels of ΣPFASs in soils ranged from 4.60 to 63.85 ng ·g-1. PFBA was the major component in water and soils, and the contribution of PFBA was 37% and 67% in water and soils, respectively. The spatial difference in ΣPFASs in the water bodies was significant. ΣPFAS concentrations in the surface water were higher in the north (mean value of 63.83 ng ·L-1) than in the south (mean value of 51.71 ng ·L-1) and higher in the eastern coastal area (mean value of 71.36 ng ·L-1) than in the western area (mean value of 36.08 ng ·L-1). ΣPFAS concentrations from upstream to downstream of the rivers showed an increasing trend. The highest PFAS concentration was found in the Chaobai River, and the lowest was detected in the South Canal. The spatial distribution of PFASs in soils was higher in the south (mean value of 13.33 ng ·g-1) than in the north (mean value of 6.38 ng ·g-1) and higher in the eastern coastal region (mean value of 11.45 ng ·g-1) than in the western region (mean value of 6.94 ng ·g-1). The soil concentrations of ΣPFASs in the Haihe River Basin were the highest. The source analysis results showed that the emulsification of rubber products, food packaging process, paper surface treatment, fire extinguishing agent use, and electrochemical fluorination process in industrial production were the main sources of PFASs in the soils in the study area. PFOS/PFOA, PFOA/PFNA, and PFHpA/PFOA analyses showed that the main source of PFASs in water bodies was the degradation of precursors. ΣPFASs in a few areas originated from the direct emissions from production, but the atmospheric deposition was small. The results of the ecological risk evaluation indicated that the exposure concentrations of PFASs in water and soils in the study area were at a low ecological risk level. However, the long-term ecological effects of PFASs cannot be ignored because of their long-distance transport capability and high food chain (web) accumulation capability.

The first complete mitochondrial DNA of the Chinese short-limbed skink (Ateuchosaurus chinensis Gray, 1845) determined by next-generation sequencing.

The complete mitochondrial DNA (mtDNA) for the Chinese short-limbed skink (Ateuchosaurus chinensis Gray, 1845) was described by using next-generation sequencing. The total length of mtDNA was 16,840 bp, which contained 13 PCGs (COI-III, ND1-6, ND4L, ATP6, ATP8, and CYTB), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region (D-loop). The Bayesian inference tree showed that A. chinensis was a sister taxon to other scincid lizards in genera of Scincella, Isopachys, Sphenomorphus and Tropidophorus. The complete mtDNA of A. chinensis will be an important genetic resource to the studies of conservation and restoration of A. chinensis.

Reduced intracellular chloride concentration impairs angiogenesis by inhibiting oxidative stress-mediated VEGFR2 activation.

Chloride (Cl-) homeostasis is of great significance in cardiovascular system. Serum Cl- level is inversely associated with the mortality of patients with heart failure. Considering the importance of angiogenesis in the progress of heart failure, this study aims to investigate whether and how reduced intracellular Cl- concentration ([Cl-]i) affects angiogenesis. Human umbilical endothelial cells (HUVECs) were treated with normal Cl- medium or low Cl- medium. We showed that reduction of [Cl-]i (from 33.2 to 16.18 mM) inhibited HUVEC proliferation, migration, cytoskeleton reorganization, tube formation, and subsequently suppressed angiogenesis under basal condition, and VEGF stimulation or hypoxia treatment. Moreover, VEGF-induced NADPH-mediated reactive oxygen species (ROS) generation and VEGFR2 axis activation were markedly attenuated in low Cl- medium. We revealed that lowering [Cl-]i inhibited the expression of the membrane-bound catalytic subunits of NADPH, i.e., p22phox and Nox2, and blunted the translocation of cytosolic regulatory subunits p47phox and p67phox, thereby restricting NADPH oxidase complex formation and activation. Furthermore, reduced [Cl-]i enhanced ROS-associated protein tyrosine phosphatase 1B (PTP1B) activity and increased the interaction of VEGFR2 and PTP1B. Pharmacological inhibition of PTP1B reversed the effect of lowering [Cl-]i on VEGFR2 phosphorylation and angiogenesis. In mouse hind limb ischemia model, blockade of Cl- efflux using Cl- channel inhibitors DIDS or DCPIB (10 mg/kg, i.m., every other day for 2 weeks) significantly enhanced blood flow recovery and new capillaries formation. In conclusion, decrease of [Cl-]i suppresses angiogenesis via inhibiting oxidase stress-mediated VEGFR2 signaling activation by preventing NADPH oxidase complex formation and promoting VEGFR2/PTP1B association, suggesting that modulation of [Cl-]i may be a novel therapeutic avenue for the treatment of angiogenic dysfunction-associated diseases.

Novel phthalide derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo.

Phthalide is a promising chemical scaffold and has been proved to show potent anti-inflammatory efficacy. In this study, three series, total of 31 novel phthalide derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. The anti-inflammatory activity of all the compounds were screened on LPS induced NO production to evaluating their inhibitory effects. Structure-activity relationship has been concluded, and finally 3-((4-((4-fluorobenzyl)oxy)phenyl)(hydroxy)methyl)-5,7-dimethoxyisobenzofuran-1 (3H)-one (compound 9o) was found to be the active one with low toxicity, which showed 95.23% inhibitory rate at 10 µM with IC50 value of 0.76 µM against LPS-induced NO over expression. Preliminary mechanism studies indicated that compound 9o activated Nrf2/HO-1 signaling pathway via accumulation ROS and blocks the NF-κB/MAPK signaling pathway. The in vivo anti-inflammatory activity shown that compound 9o had obvious therapeutic effect against the adjuvant-induced rat arthritis model.

Hepatocyte TMEM16A Deletion Retards NAFLD Progression by Ameliorating Hepatic Glucose Metabolic Disorder.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease, and the mechanisms underpinning its pathogenesis have not been completely established. Transmembrane member 16A (TMEM16A), a component of the Ca2+-activated chloride channel (CaCC), has recently been implicated in metabolic events. Herein, TMEM16A is shown to be responsible for CaCC activation in hepatocytes and is increased in liver tissues of mice and patients with NAFLD. Hepatocyte-specific ablation of TMEM16A in mice ameliorates high-fat diet-induced obesity, hepatic glucose metabolic disorder, steatosis, insulin resistance, and inflammation. In contrast, hepatocyte-specific TMEM16A transgenic mice exhibit the opposite phenotype. Mechanistically, hepatocyte TMEM16A interacts with vesicle-associated membrane protein 3 (VAMP3) to induce its degradation, suppressing the formation of the VAMP3/syntaxin 4 and VAMP3/synaptosome-associated protein 23 complexes. This leads to the impairment of hepatic glucose transporter 2 (GLUT2) translocation and glucose uptake. Notably, VAMP3 overexpression restrains the functions of hepatocyte TMEM16A in blocking GLUT2 translocation and promoting lipid deposition, insulin resistance, and inflammation. In contrast, VAMP3 knockdown reverses the beneficial effects of TMEM16A downregulation. This study demonstrates a role for TMEM16A in NAFLD and suggests that inhibition of hepatic TMEM16A or disruption of TMEM16A/VAMP3 interaction may provide a new potential therapeutic strategy for NAFLD.

Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R- group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R- group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R- group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.

Stability and stabilization of (-)-gallocatechin gallate under various experimental conditions and analyses of its epimerization, auto-oxidation, and degradation by LC-MS.

BACKGROUND: (-)-Gallocatechin gallate (GCG) shows multi-bioactivities. Its stability, however, has not been investigated systematically yet. Therefore, the objective of this study was to characterize the stability of GCG and to find ways to stabilize it in biological assays. Furthermore, the epimerization of the compound, its auto-oxidation and degradation were also analyzed by liquid chromatography mass spectrometry (LC-MS). RESULTS: The stability of GCG was concentration-dependent and was sensitive to pH, temperature, bivalent cations, and dissolved oxygen level. The results also showed that GCG was not stable in common buffers (50 mmol L-1 , pH 7.4, 37 °C) or in cell culture medium DMEM/F12 under physiological conditions (pH 7.4, 37 °C). Our experiments indicated that nitrogen-saturation and the addition of ascorbic acid (VC) could stabilize GCG in biological assays. In addition, LC-MS determination indicated that GCG was able to be epimerized to its epimer (-)-epigallocatechin gallate (EGCG). Meanwhile it was also able to be auto-oxidized to theasinensin and compound P2 and degraded to gallocatechin and gallic acid in pure water at 100 °C. CONCLUSION: The stability of GCG should be seriously considered in research on the bioactivity of it to avoid possible artifacts. Nitrogen-saturation and use of VC are good ways to make GCG stable in biological assays. © 2019 Society of Chemical Industry.

What is the most relevent factor causing pain during ALA-PDT? A multi-center, open clinical pain score research trial of actinic keratosis, acne and condylomata acuminata.

BACKGROUND: To date, it has been reported that the intrinsic factors(lesions location, lesions area, disease tynpes) and extrinsic factors(fluence rate) contribute to the pain during 5-aminolevulinic acid photodynamic therapy (ALA-PDT). But there are few studies on pain during ALA-PDT and lack of sufficient clinical evidence related to the pain intensity. OBJECTIVE: To investigate pain intensity and its relative factors during ALA-PDT and to provide clinical implication. METHODS: The pain numeric rating scale (PNRS) score was used to evaluate the patients' pain intensity at different times during ALA-PDT irradiation from 0 to 10 min during treatment. Gender, age, lesions location, lesions area, ALA concentration and fluence rate were recored. RESULTS: The trial enrolled 274 patients in total, including 118 acne patients (in face), 30 actinic keratosis(AK)patients(in face), 126 Condylomatata acuminate patients(in genitalia). The average pain score in PDT was highest in the patients with actinic keratosis(7.3 ± 0.7), and that of condylomata acuminata was the lowest (4.5 ± 1.1) (p < 0.05). The highest pain score in patients with AK, acne and condylomata acuminata was 8, 6 and 6 respectively which occurred at 4 min, 4 min and 6 min respectively. The pain score of males was higher compared with females in all of the three diseases (p < 0.05). The pain score of facial diseases (5.6 ± 1.2) was higher than that of the genitalia (4.5 ± 1.1) (p < 0.05). The lesions area was positively correlated with the pain score (p < 0.05). In facial diseases, the pain score of patients with high fluence rate (7.3 ± 0.7) was higher than patients with low fluence rate (5.1 ± 0.9) (p < 0.05). CONCLUSIONS: Intrinsic and extrinsic factors both correlate with pain during PDT. Intrinsic factors are difficult to change, so extrinsic factors are the key point to control. We can reduce the fluence rate and extend the treatment time, relieving pain intensity while still ensuring equivalent efficacy.

[Coagulation function and hemorrhagic diseases in preterm infants with different gestational ages].

OBJECTIVE: To study the correlation between coagulation function and gestational age in preterm infants and the possible value of coagulation function measurement in predicting hemorrhagic diseases. METHODS: The clinical data of preterm infants who were hospitalized between September 2016 and August 2017 were collected. The coagulation indicators were measured within 2 hours after birth. According to the gestational age, the preterm infants were divided into late preterm infant group (n=322), early preterm infant group (n=241) and extremely/very early preterm infant group (n=128). Coagulation function was compared among the three groups, as well as between the preterm infants with and without hemorrhagic diseases within 3 days after birth. RESULTS: There were significant differences in thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) and D-dimer (DD) among the three groups (P<0.05). APTT, PT, FDP and DD were negatively correlated with gestational age, while TT was positively correlated with gestational age (P<0.05). The preterm infants with hemorrhagic diseases had a longer APTT and a higher level of DD (P<0.05). CONCLUSIONS: Coagulation function gradually becomes mature in preterm infants with the increase in gestational age. Abnormal APTT and DD indicate that preterm infants may have a higher risk of hemorrhagic diseases.

[Characteristics of Nitrogen and Phosphorus Formation in Atmospheric Deposition in Dianchi Lake and Their Contributions to Lake Loading].

To examine the effects of seasonal changes and precipitation on the concentrations of various nitrogen and phosphorus forms in Dianchi Lake, the concentrations of various nitrogen and phosphorus forms of atmospheric deposition were determined by UV spectrophotometry. Additionally, the contributions of nitrogen and phosphorus to water pollution in Dianchi Lake were discussed. The results showed that the atmospheric depositional nitrogen concentration in Dianchi Lake is generally consistent with the characteristics of the low rainy season and high dry season. The nitrogen and phosphorus load of atmospheric deposition was positively correlated with rainfall. Seasonal changes were mainly characterized by low dry season and high rainy season. The atmospheric depositional nitrogen load was dominated by dissolved inorganic nitrogen, which accounted for 63.70% of the total nitrogen deposition load. The phosphorus load was mainly PP, which accounted for 45.54% of the total phosphorus precipitation load. Excessive fertilization and loss of nitrogen and phosphorus from fertilizers are the major sources of nitrogen and phosphorus in atmospheric wet deposition. Combined with data from rivers entering the lake, the settlements of TN and TP in the atmospheric deposition of Dianchi Lake were 6.14% and 12.76% of the river load, respectively. Therefore, the primary source of pollution in Dianchi Lake was still the load brought by the river into the lake. However, the nitrogen and phosphorus fluxes in the atmospheric deposition of Dianchi Lake were at intermediate levels compared with other regions, so this contribution requires further investigation.

Orobanone analogues from acid-promoted aromatization rearrangement of curcumol inhibit hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays.

In this paper, the mechanism of orobanone analogues formation via aromatization rearrangement of curcumol was minutely explored. Aromatization of curcumol with acetone under acidic condition was selected as the model reaction. The formation of a stable aromatic system was the driving force for this reaction. Based on the model reaction, other four new orobanone analogues were prepared through curcumol reacting with different carbonyl compounds. The results showed that the stability of carbocation, which was generated from the carbonyl compounds, and the steric hindrance were main factors affecting the aromatization. We also synthesized the analogue of aromaticane B using compound 2. In vitro anti-proliferative activity of some derivatives were tested by MTT assay. Two derivatives showed weak anti-tumor effect on two cancer cell lines (HepG2 and MCF7) under normoxia. Four orobanone analogue 2, 5, 6 and 9 significantly inhibited hypoxia-induced HIF-1 luciferase reporter activity in HeLa cells with the IC50 values of 13.6, 6.6, 2.4 and 18.2 µM, respectively.

Exposure to Radon and Kidney Cancer: A Systematic Review and Meta-analysis of Observational Epidemiological Studies.

OBJECTIVE: To evaluate the possible association between radon exposure and kidney cancer. METHODS: We performed a systematic review and a meta-analysis based on random effect models to provide a pooled association measure. RESULTS: We subjected 8 studies (overall relative risks and 95% confidence intervals: 1.01, 0.72 to 1.43, I2 = 64.4%) to meta-analysis. Subgroup analysis revealed a marginally significant association between radon exposure and kidney cancer in studies conducted in Europe. Two population-based studies provided no evidence for the increased risk of kidney cancer in the general population. CONCLUSION: The association between radon and kidney cancer remains unclear but cannot be excluded because of its biological plausibility and the limited number and quality of existing studies. Additional data from the general population and well-designed miner cohort studies are needed to reveal the real relationship between radon exposure and kidney cancer.