Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 81
Filter
1.
J Hosp Infect ; 150: 72-82, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782053

ABSTRACT

We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled odds ratios (ORs), based on sample size, the P-value of Egger's test and heterogeneity among studies. Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% confidence interval (CI), 1.20-1.41) or hypertension (OR, 1.26; 95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (body mass index ≥30 kg/m2) (OR, 1.42; 95% CI, 1.28-1.57), those who were male (OR, 1.65; 95% CI, 1.12-2.44), those who had an American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.02; 95% CI, 1.02-3.99) and those who had a history of smoking (OR, 2.44; 95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy.

3.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(8): 1297-1305, 2023 Aug 20.
Article in Chinese | MEDLINE | ID: mdl-37712265

ABSTRACT

OBJECTIVE: To investigate the inhibitory effect of dealcoholized red wine (DRW) on occurrence and progression of hepatocellular carcinoma (HCC) and explore its possible mechanisms. METHODS: Three HCC cell lines (Huh7, HepG2 and SKHep-1) treated with 5, 10, 25, 50 and 100 µL/mL DRW were examined for changes in proliferation and colony formation ability using CCK-8 assay and colony formation assay. A nude mouse model bearing subcutaneous HCC xenograft was used to test the effect of 300 µL/day DRW for 4 weeks on tumor growth. The inhibitory effect of 300 µL/day DRW for 6 weeks on tumor growth was also observed in a mouse model of chemically induced HCC by examining the tumor number, largest tumor diameter and the liver/body ratio. RNA-seq technique was used for transcriptome sequencing of Huh7 cells treated with DRW (75 µL/mL) for 48 h, and gene-set enrichment analysis (GSEA) was performed to identify the changes in genes and pathways. Flow cytometry assay was used to analyze the changes in cell cycle and apoptosis of the cells. RESULTS: DRW inhibited the proliferation of the HCC cell lines in a concentration-and time-dependent manner, and concentration-dependently inhibited colony formation of the cells. Treatment with DRW significantly reduced the volume of subcutaneous tumor xenograft in the tumor-bearing nude mice (P < 0.05), and lowered the number of tumors (P < 0.001), the largest tumor diameter (P < 0.05) and the liver/body ratio (P < 0.01) in mice with chemically induced HCC. RNA-seq showed that 634 genes were significantly up-regulated and 478 were down-regulated in Huh7 cells after treatment with DRW. Gene-set enrichment analysis revealed that DRW significantly down-regulated cell cycle-related pathways (E2F Targets, G2M Checkpoint and MYC Targets) and up-regulated apoptosis pathways. Flow cytometry assay showed that DRW induced cell cycle arrest in G1 phase and apoptosis of Huh7 cells. CONCLUSION: DRW inhibits the occurrence and progression of HCC, and this effect is mediated possibly by inducing cell cycle arrest and apoptosis.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Wine , Humans , Animals , Mice , Mice, Nude , Cell Cycle Checkpoints , Apoptosis , Disease Models, Animal
4.
J Med Chem ; 66(17): 12324-12341, 2023 09 14.
Article in English | MEDLINE | ID: mdl-37647129

ABSTRACT

A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxic agents, conjugated to the ß-position of the Michael acceptor, via an addition-elimination mechanism promoted by covalent binding. Studies on model systems showed that conjugated 5-fluorouracil (5FU) could be released upon thiol addition in relevant time scales. A series of covalent epidermal growth factor receptor (EGFR) inhibitors were synthesized as their 5FU derivatives. Achieving the desired release of 5FU was demonstrated to depend on the electronics and geometry of the compounds. Mass spectrometry and NMR studies demonstrated an anilinoquinazoline acrylate ester conjugate bound to EGFR with the release of 5FU. This work establishes that acrylates can be used to release conjugated molecules upon covalent binding to proteins and could be used to develop targeted therapeutics.


Subject(s)
Cytotoxins , Fluorouracil , Fluorouracil/pharmacology , ErbB Receptors , Esters , Mass Spectrometry
5.
Bioorg Med Chem ; 91: 117387, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37418825

ABSTRACT

Ureas are an important functional group in small molecule drugs as well as having wider applications in organic chemistry. Understanding of their conformation is of critical importance for rational design of urea-containing bioactive compounds. Whilst the conformational preferences of biaryl ureas have been extensively studied, very little attention has been paid to alkylated analogues. We carried out a systematic study of N-aryl (phenyl and pyridyl)-N'-cyclopentyl ureas with differing N-methylation patterns using Well Tempered Metadynamics at a semi-empirical level in implicit water (GBSA) using Well-Tempered Metadynamics to generate their conformational free-energy landscapes. Geometries and energetics of the most relevant configurations are further refined using DFT level of theory. Validation for the computation was obtained by synthesis of all 8 analogues followed by conformational studies by X-ray crystallography and NMR. These findings reveal that the methylation pattern significantly affects the conformational preference of the system. Most notably, N-phenyl-N'-cyclopentyl urea is shown to adopt both the trans-trans, and cis-trans conformations with equal energy and that the cis-trans conformation can be significantly stabilised by the presence of an internal hydrogen bond to the N'-hydrogen. This study will be of utility for the design of N-alkyl-N'-aryl ureas as drug candidates.


Subject(s)
Hydrogen , Urea , Molecular Conformation , Magnetic Resonance Spectroscopy , Hydrogen/chemistry , Drug Discovery
6.
Eur Rev Med Pharmacol Sci ; 27(24): 11988-12003, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38164861

ABSTRACT

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.


Subject(s)
Benzbromarone , Febuxostat , Gout Suppressants , Gout , Uricosuric Agents , Humans , Allopurinol/therapeutic use , Benzbromarone/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , China , Febuxostat/therapeutic use , Gout/drug therapy , Gout Suppressants/therapeutic use , Hyperuricemia , Treatment Outcome , Uric Acid , Uricosuric Agents/therapeutic use
7.
Rev Sci Instrum ; 93(9): 093523, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36182514

ABSTRACT

Bright, short-pulsed neutron beams from laser-driven neutron sources (LANSs) provide a new perspective on material screening via fast neutron activation analysis (FNAA). FNAA is a nondestructive technique for determining material elemental composition based on nuclear excitation by fast neutron bombardment and subsequent spectral analysis of prompt γ-rays emitted by the active nuclei. Our recent experiments and simulations have shown that activation analysis can be used in practice with modest neutron fluences on the order of 105 n/cm2, which is available with current laser technology. In addition, time-resolved γ-ray measurements combined with picosecond neutron probes from LANSs are effective in mitigating the issue of spectral interference between elements, enabling highly accurate screening of complex samples containing many elements. This paper describes the predictive capability of LANS-based activation analysis based on experimental demonstrations and spectral calculations with Monte Carlo simulations.

8.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(2): 163-171, 2022 Apr 12.
Article in Chinese | MEDLINE | ID: mdl-35537838

ABSTRACT

OBJECTIVE: To create a risk assessment indicator system for re-establishment of imported malaria. METHODS: The risk assessment indicator system for re-establishment of imported malaria was preliminarily constructed through literature review and thematic discussions. A total of 26 malaria control experts were selected to carry out a two-round Delphi consultation of the indicator system. The active coefficient, authority coefficient and coordination coefficient of the experts and the coefficient of variation on each indicator were calculated for indicator screening and the weight of each indicator was calculated. The reliability of the indicator system was evaluated using Cronbach's coefficient α, and the content validity of the indicator system was evaluated using the authority coefficient of the expert, while the structural validity of the indicator system was evaluated using Kaiser-Meyer-Olkin (KMO) test and factor analysis. RESULTS: Two rounds of Delphi expert consultations were completed by 23 malaria control experts, and a risk assessment indicator system for re-establishment of imported malaria was constructed, including 3 primary indicators, 7 secondary indicators, and 21 tertiary indicators. The active coefficient (100.00% vs. 88.46%; P < 0.01) and coordination coefficient of the expert (0.372 vs. 0.286; P < 0.01) were significantly greater in the second round of the Delphi expert consultation than in the first round. After the second round of the Delphi expert consultation, the authority coefficient of the experts ranged from 0.757 to 0.930 on each indicator, and the coefficients of variation were 0.098 to 0.136, 0.112 to 0.276 and 0.139 to 0.335 for the primary, secondary and tertiary indicators, respectively. The overall Cronbach's coefficient α of the indicator system was 0.941, and there were significant differences in the KMO values for primary (KMO value = 0.523; χ2 = 18.192, P < 0.05), secondary (KMO value = 0.694, χ2 = 51.499, P < 0.01) and tertiary indicators (KMO value = 0.519; χ2 = 477.638, P < 0.01), while the cumulative contribution rate of six principal components in the tertiary indicators was 84.23%. The normalized weights of three primary indicators of the source of infection, transmission condition and control capability were 0.337, 0.333 and 0.329, and the three secondary indicators with the greatest normalized weights included the number of imported cases and malaria parasite species (0.160), introduction of imported cases in China and medical care seeking (0.152), vector species and density (0.152), while the five tertiary indicators with the greatest normalized weights included the malaria parasite species of imported cases (0.065), vector populations (0.064), and the time interval from onset to medical care seeking (0.059), number of imported cases (0.056), and the time interval from medical care seeking to definitive diagnosis (0.055). CONCLUSIONS: A risk assessment indicator system for re-establishment of imported malaria is successfully created, which provides insights into the assessment of the risk of re-establishment of imported malaria and management of key high-risk factors in malaria-eliminated areas.


Subject(s)
Malaria , China/epidemiology , Delphi Technique , Humans , Malaria/prevention & control , Reproducibility of Results , Risk Assessment , Risk Factors
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(2): 181-189, 2022 Feb 20.
Article in Chinese | MEDLINE | ID: mdl-35365441

ABSTRACT

OBJECTIVE: To explore the effect of transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. METHODS: Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. RESULTS: TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). CONCLUSION: Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.


Subject(s)
Asthma , Toluene 2,4-Diisocyanate , Animals , Mice , Asthma/chemically induced , Inflammation , Macrophages , Receptor-Interacting Protein Serine-Threonine Kinases , Respiratory System , Toluene 2,4-Diisocyanate/adverse effects
10.
Fa Yi Xue Za Zhi ; 37(4): 533-538, 2021 Aug.
Article in Chinese | MEDLINE | ID: mdl-34726008

ABSTRACT

ABSTRACT: Objective To study the preference relation between residence, sex, age and causes of accidental death of Chinese residents. Methods In this study, 72 residence-sex-age groups and 8 causes of accidental death were qualitatively and quantitatively analyzed by correspondence analysis using the official statistical yearbook issued from 2014 to 2018, and the preference values were calculated. Results Among the 576 pairs of correspondences between the residence-sex-age groups and causes of accidental death, 352 pairs (61.11%) showed a preference relation (preference value>0). In terms of residence and sex, accidental death preference among Chinese residents was higher in rural areas than in urban areas, and males were higher than females. In terms of the causes of accidental death, the overall risk of accidental mechanical asphyxia and motor vehicle accidents was the highest among all age groups of Chinese residents. In terms of age, with the increase of age, the preference value of accidental death of Chinese residents showed a trend of first increasing and then decreasing. The comparative analysis results of the preference values of various causes of accidental death in different age groups showed that motor vehicle traffic accidents, accidental poisoning, death by crush and electric shock were more likely to occur in the working age group between 20 and 59 years old, accidental fall and fire were more likely to occur in the elderly group over 80 years old, and drowning and accidental mechanical asphyxia were more likely to occur in the minor group between 1 and 19 years old. Conclusion There are different preference relations between residence-sex-age groups and causes of accidental death in China. Therefore, effective control strategies and measures should be formulated for Chinese residents with preference for accidental death.


Subject(s)
Drowning , Accidental Falls , Accidents, Traffic , Adult , Aged , Asphyxia/etiology , China/epidemiology , Female , Humans , Male , Middle Aged , Young Adult
12.
J Med Chem ; 64(14): 10001-10018, 2021 07 22.
Article in English | MEDLINE | ID: mdl-34212719

ABSTRACT

NF-κB-inducing kinase (NIK) is a key enzyme in the noncanonical NF-κB pathway, of interest in the treatment of a variety of diseases including cancer. Validation of NIK as a drug target requires potent and selective inhibitors. The protein contains a cysteine residue at position 444 in the back pocket of the active site, unique within the kinome. Analysis of existing inhibitor scaffolds and early structure-activity relationships (SARs) led to the design of C444-targeting covalent inhibitors based on alkynyl heterocycle warheads. Mass spectrometry provided proof of the covalent mechanism, and the SAR was rationalized by computational modeling. Profiling of more potent analogues in tumor cell lines with constitutively activated NIK signaling induced a weak antiproliferative effect, suggesting that kinase inhibition may have limited impact on cancer cell growth. This study shows that alkynyl heterocycles are potential cysteine traps, which may be employed where common Michael acceptors, such as acrylamides, are not tolerated.


Subject(s)
Alkynes/pharmacology , Cysteine/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrimidines/pharmacology , Alkynes/chemical synthesis , Alkynes/chemistry , Cysteine/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Serine-Threonine Kinases/metabolism , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , NF-kappaB-Inducing Kinase
13.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(3): 274-280, 2021 Jul 05.
Article in Chinese | MEDLINE | ID: mdl-34286529

ABSTRACT

OBJECTIVE: To understand the density, populations and habitats of malaria vector Anopheles in Guizhou Province from 2005 to 2019, so as to provide the evidence for formulating the countermeasures to tackle the risk of local transmission of imported malaria in the province. METHODS: The malaria vector Anopheles density and populations were monitored using human bait trapping and light trapping techniques in Guizhou Province from 2005 to 2019, and all captured Anopheles was morphologically identified and counted. In addition, the distribution of Anopheles habitats was investigated. RESULTS: During the period from 2005 through 2019, the malaria vector Anopheles density increased from early June in Guizhou Province, peaked on early July and then declined, which appeared a single peak. The greatest Anopheles density was seen on early August, 2018 [57.34 mosquitoes/(person-night)], and the lowest density was found on late October, 2009 [1.29 mosquitoes/(person-night)]. The annual mean Anopheles density slowly reduced from 17.91 mosquitoes/(person-night) in 2005 to 12.34 mosquitoes/(person-night) in 2012, with a 38.02% reduction (χ2trend = 115.04, P < 0.01), while the annual mean Anopheles density showed a tendency towards a rise from 2017 to 2019 (χ2trend = 420.00, P < 0.01). The malaria vector Anopheles was captured during the period between 19 : 00 and 7 : 00 of the next day in Guizhou Province from 2017 to 2019, with the overall density appearing a tendency towards a rise followed by a decline, and the Anopheles activity was highly frequent during the period between 19 : 00 and 21 : 00. The malaria vector Anopheles was monitored for 938 times using the light trapping method in Guizhou Province from 2005 to 2019, and a total of 52 781 Anopheles mosquitoes were captured, including 49 705 An. sinensis, 804 An. minimus, 238 An. anthropophagus, and 2 034 other Anopheles mosquitoes, with a significant difference seen in the Anopheles composition (χ2 = 165.68, P < 0.01). From 2017 to 2019, a total of 24 557 Anopheles mosquitoes were captured in human housings, outdoors and livestock housings in Guizhou Province, with 67.65% captured in livestock housings and 12.01% in human housings, and there was a significant difference in the number of Anopheles mosquitoes captured from the three types of habitats (χ2 = 55.04, P < 0.01). An. sinensis, An. minimus and An. anthropophagus were captured form all three types of habitats, in which 98.07% was An. sinensis, and 0.09% was An. anthropophagus. CONCLUSIONS: The population structure of malaria vector Anopheles has changed in historically malaria-endemic areas of Guizhou Province, and An. sinensis has replaced An. minimus and An. anthropophagus to become the predominant malaria vector. The malaria vector Anopheles density has shown a tendency towards a rise in Guizhou Province during the recent years, and there have been a rise in the type and number of Anopheles mosquitoes, leading to a potential risk of local transmission of imported malaria. Long-term, persistent and extensive surveillance of malaria vectors is recommended in Guizhou Province.


Subject(s)
Anopheles , Malaria , Animals , Humans , Malaria/epidemiology , Mosquito Vectors
14.
Zhonghua Zhong Liu Za Zhi ; 42(12): 1020-1024, 2020 Dec 23.
Article in Chinese | MEDLINE | ID: mdl-33342158

ABSTRACT

Objective: To explore the learning curve of central pancreatectomy (CP) and provide an excellent reference for surgeons to get the point of this operation. Methods: Clinical data of 73 patients who underwent CP in the same operation team from January 2006 to January 2018 were collected and retrospectively analyzed by the moving average method (MAM) and the cumulative sum method (CUSUM). Data was analyzed by statistical package for social science (SPSS) software. Results: According to the MAM and CUSUM curves, the learning process of CP could be divided into two stages. At the first stage (n=1-11), the median operation time was 340 minutes and the median intraoperative hemorrhage was 400 ml. In the second stage (n=12-73), the median operation time was 213 minutes and the median intraoperative hemorrhage was 100 ml. The difference was statistically significant (P<0.001). There were no significant differences between the two stages of patients in terms of other aspects (P>0.05). Conclusions: CP can be mastered after 11 cases of exercises. In the first 11 operations, surgeons should get familiar with the operation process, respond actively to emergencies and accumulate experience to gain this surgical technique fast.


Subject(s)
Learning Curve , Pancreatectomy , Surgeons , Blood Loss, Surgical/statistics & numerical data , Humans , Operative Time , Retrospective Studies , Surgeons/psychology
15.
Sci Rep ; 10(1): 20157, 2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33214592

ABSTRACT

The scientific and technical advances continue to support novel discoveries by allowing scientists to acquire new insights into the structure and properties of matter using new tools and sources. Notably, neutrons are among the most valuable sources in providing such a capability. At the Institute of Laser Engineering, Osaka, the first steps are taken towards the development of a table-top laser-driven neutron source, capable of producing a wide range of energies with high brightness and temporal resolution. By employing a pure hydrogen moderator, maintained at cryogenic temperature, a cold neutron ([Formula: see text]) flux of [Formula: see text]/pulse was measured at the proximity of the moderator exit surface. The beam duration of hundreds of ns to tens of [Formula: see text] is evaluated for neutron energies ranging from 100s keV down to meV via Monte-Carlo techniques. Presently, with the upcoming J-EPoCH high repetition rate laser at Osaka University, a cold neutron flux in orders of [Formula: see text] is expected to be delivered at the moderator in a compact beamline.

17.
Hum Exp Toxicol ; 38(5): 598-609, 2019 May.
Article in English | MEDLINE | ID: mdl-30744404

ABSTRACT

The aim of this study was to identify biomarkers of zoledronate-induced nephrotoxicity and to further characterize the mechanisms underlying this process by analyzing urinary metabolites. Twenty-four rats were randomly divided into four groups containing four (two control groups) or eight rats (two zoledronate groups) per group. The rats were injected intravenously with saline or zoledronate (3 mg/kg) singly (single, 3 weeks) or repeatedly eight times (3 weeks/time, 24 weeks). Serum blood urea nitrogen, serum creatinine, creatinine clearance, and kidney injury observed by hematoxylin and eosin and immunohistochemical staining were changed only in the repeated zoledronate group (3 mg/kg, 3 weeks/time, 24 weeks). Urinary levels of S-adenosylmethionine, S-adenosylhomocysteine, l-cystathionine, l-γ-glutamylcysteine, and glutathione related to glutathione metabolism and fumaric acid and succinic acid related to the tricarboxylic acid cycle in the zoledronate-treated group (3 mg/kg, 3 weeks/time, 24 weeks) were significantly lower than those in the control group, suggesting that zoledronate may cause cellular oxidative stress. Besides, urinary levels of uracil and uridine related to pyrimidine metabolism also decreased after zoledronate treatment (3 mg/kg, 3 weeks/time, 24 weeks), while the levels of hypoxanthine related to purine metabolism, histamine related to histamine metabolism, and several amino acids were significantly increased. Moreover, zoledronate-induced enhanced oxidative stress and histamine overproduction were confirmed by reactive oxygen species (ROS) and histamine measurement in a human proximal tubular cell line. Taken together, zoledronate-induced nephrotoxicity may be attributed to it inducing perturbations in glutathione biosynthesis and the tricarboxylic acid cycle, further causing ROS overproduction, oxidative stress, and cellular inflammation, thereby leading to nephrotoxicity.


Subject(s)
Bone Density Conservation Agents/toxicity , Kidney Diseases/chemically induced , Zoledronic Acid/toxicity , Animals , Biomarkers/urine , Blood Urea Nitrogen , Cell Line , Creatinine/blood , Glutathione/urine , Histamine/metabolism , Humans , Kidney/drug effects , Kidney/pathology , Kidney Diseases/pathology , Kidney Diseases/urine , Male , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism
18.
Zhonghua Yi Xue Za Zhi ; 97(37): 2928-2931, 2017 Oct 10.
Article in Chinese | MEDLINE | ID: mdl-29050164

ABSTRACT

Objective: By the preliminary comparison study on the constituent ratio and clinical characteristics of polycystic ovary syndrome (PCOS) in Tibetan and Han women in Tibetan Plateau, we aimed to find the relevance of its pathogenic factors, and to guide the treatment of PCOS in the plateau region and improve the prognosis. Methods: The general situation and clinical data of 165 patients who were diagnosed with PCOS from December 1, 2015 to November 30, 2016 in the Department of Obstetrics and Gynecology of the People's Hospital of Tibet Autonomous Region were analyzed retrospectively. The prevalence of PCOS among Tibetan and Han women in Tibetan Plateau were compared. Results: (1) A total of 1 520 patients were treated in the Tibet Autonomous Region People's Hospital gynecological endocrinology clinics in one year (Tibetan 865 cases, Han 617 cases, other ethnic groups 38 cases), of which patients with PCOS accounted for 10.9% (165/1520). (2) The incidence of Tibetan PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 21.2% (35/165), 20.6% (34/165), 16.4% (27/165), 28.5% (47/165), 17% (28/165), 38.2% (63/165), 23.6% (39/165), and 36.4% (60/165), respectively. The incidence of Han PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 7.9% (13/165), 10.3% (17/165), 9.1% (15/165), 15.2% (25/165), 9.7% (16/165), 14.5% (24/165), 10.9% (18/165) and 19.4% (32/165), respectively. The proportion of high testosterone in Tibetan PCOS patients was higher than that in Han PCOS patients with statistically significant. (3) The chief complaint of Tibetan PCOS patients were oligomenorrhea and infertility, and the chief complaint of Han PCOS patients were infertility and amenorrhea. (4) The constituent ratio of outpatient clinics in Nyingchi who were with PCOS at an average elevation of about 3 000 meters in the Tibetan Plateau was 7.9% (13/165), and the average constituent ratio in Lhasa, Xigatse and Nagqu over 3 500 meters above sea level was 35.8% (59/165), 16.9% (28/165) and 15.8% (26/165), respectively. Conclusion: The prevalence of PCOS in Tibetan areas is slightly higher than that in the international community. The clinical manifestations of Tibetan patients with PCOS are significantly different from those of Han patients with PCOS. The higher the altitude, the higher the incidence of PCOS.


Subject(s)
Polycystic Ovary Syndrome , Female , Humans , Pregnancy , Prevalence , Retrospective Studies , Tibet , Waist Circumference
19.
J Chem Phys ; 146(21): 214304, 2017 Jun 07.
Article in English | MEDLINE | ID: mdl-28595406

ABSTRACT

A first principles quantum dynamics study of N-H photodissociation of pyrrole on the S0-1πσ*(A21) coupled electronic states is carried out with the aid of an optimally designed UV-laser pulse. A new photodissociation path, as compared to the conventional barrier crossing on the πσ*1 state, opens up upon electronic transitions under the influence of pump-dump laser pulses, which efficiently populate both the dissociation channels. The interplay of electronic transitions due both to vibronic coupling and the laser pulse is observed in the control mechanism and discussed in detail. The proposed control mechanism seems to be robust, and not discussed in the literature so far, and is expected to trigger future experiments on the πσ*1 photochemistry of molecules of chemical and biological importance. The design of the optimal pulses and their application to enhance the overall dissociation probability is carried out within the framework of optimal control theory. The quantum dynamics of the system in the presence of pulse is treated by solving the time-dependent Schrödinger equation in the semi-classical dipole approximation.

20.
Eur Rev Med Pharmacol Sci ; 21(8): 1774-1779, 2017 04.
Article in English | MEDLINE | ID: mdl-28485803

ABSTRACT

OBJECTIVE: To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. PATIENTS AND METHODS: The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. RESULTS: The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). CONCLUSIONS: Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.


Subject(s)
Epilepsy, Temporal Lobe/surgery , Radiosurgery/methods , Adolescent , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...