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1.
Org Biomol Chem ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283052

ABSTRACT

Cleavage of the C-N bond of a secondary amide could provide alternative access to primary amides; however, this strategy remains challenging due to oxidation resistance of the amide. Herein, we employed the cobalt(II)/Oxone catalytic system, one of the advanced oxidation processes (AOPs), to make it available to break the strong C-N bond of various secondary (sulfon)amides, especially those bearing electron-poor or ortho-substituted N-arenes, en route to desirable primary (sulfon)amides. Control experiments showed that it was probably not the generally-considered persulfate anion radical in the cobalt/peroxymonosulfate (Co/PMS) system but the proposed high-valent cobalt-oxo intermediate that should be the major active species for the initial N-H oxidation of N-aryl amides. In the case of N-alkylated secondary amides, the α-C-H bond, rather than the N-H bond, should be oxidized first by both the reactive radicals and high-valent cobalt-oxo species. This work not only establishes an efficient method for removing the N-substituents of secondary amides at low cost, with readily available and eco-friendly reagents, but also demonstrates further synthetic application and provides more insight into intermediates for metal-based AOPs in environmental remediation.

2.
J Agric Food Chem ; 72(31): 17191-17199, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39054861

ABSTRACT

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has a high status in the development of new inhibitors. To develop novel and highly effective PPO inhibitors, active substructure linking and bioisosterism replacement strategies were used to design and synthesize novel tetrahydrophthalimide derivatives containing oxadiazole/thiadiazole moieties, and their inhibitory effects on Nicotiana tobacco PPO (NtPPO) and herbicidal activity were evaluated. Among them, compounds B11 (Ki = 9.05 nM) and B20 (Ki = 10.23 nM) showed significantly better inhibitory activity against NtPPO than that against flumiclorac-pentyl (Ki = 46.02 nM). Meanwhile, compounds A20 and B20 were 100% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) at 37.5 g a.i./ha. It was worth observing that compound B11 was more than 90% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) at 18.75 and 9.375 g a.i./ha. It was also safer to rice, maize, and wheat than flumiclorac-pentyl at 150 g a.i./ha. In addition, the molecular docking results showed that compound B11 could stably bind to NtPPO and it had a stronger hydrogen bond with Arg98 (2.9 Å) than that of flumiclorac-pentyl (3.2 Å). This research suggests that compound B11 could be used as a new PPO inhibitor, and it could help control weeds in agricultural production.


Subject(s)
Amaranthus , Drug Design , Enzyme Inhibitors , Herbicides , Molecular Docking Simulation , Oxadiazoles , Phthalimides , Plant Weeds , Protoporphyrinogen Oxidase , Thiadiazoles , Herbicides/chemistry , Herbicides/pharmacology , Herbicides/chemical synthesis , Thiadiazoles/chemistry , Thiadiazoles/pharmacology , Thiadiazoles/chemical synthesis , Plant Weeds/drug effects , Plant Weeds/enzymology , Oxadiazoles/chemistry , Oxadiazoles/pharmacology , Oxadiazoles/chemical synthesis , Structure-Activity Relationship , Phthalimides/chemistry , Phthalimides/pharmacology , Phthalimides/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Protoporphyrinogen Oxidase/antagonists & inhibitors , Protoporphyrinogen Oxidase/chemistry , Protoporphyrinogen Oxidase/metabolism , Amaranthus/chemistry , Amaranthus/drug effects , Plant Proteins/chemistry , Plant Proteins/antagonists & inhibitors , Molecular Structure , Nicotiana/chemistry
3.
J Agric Food Chem ; 72(22): 12425-12433, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38781442

ABSTRACT

Phytoene desaturase (PDS) is a critical functional enzyme in blocking ζ-carotene biosynthesis and is one of the bleaching herbicide targets. At present, norflurazon (NRF) is the only commercial pyridazine herbicide targeting PDS. Therefore, developing new and diverse pyridazine herbicides targeting PDS is urgently required. In this study, diflufenican (BF) was used as the lead compound, and a scaffold-hopping strategy was employed to design and synthesize some pyridazine derivatives based on the action mode of BF and PDS. The preemergence herbicidal activity tests revealed that compound 6-chloro-N-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenoxy)pyridazine-4-carboxamide (B1) with 2,4-diF substitution in the benzeneamino ring showed 100% inhibition rates against the roots and stems of Echinochloa crus-galli and Portulaca oleracea at 100 µg/mL, superior to the inhibition rates of BF. Meanwhile, compound B1 demonstrated excellent postemergence herbicidal activity against broadleaf weeds, which was similar to that of BF (inhibition rate of 100%) but superior to that of NRF. This indicated that 6-Cl in the pyridazine ring is the key group for postemergence herbicidal activity. In addition, compound B1 could induce downregulation of PDS gene expression, 15-cis-phytoene accumulation, and Y(II) deficiency and prevent photosynthesis. Therefore, B1 can be considered as a promising candidate for developing high-efficiency PDS inhibitors.


Subject(s)
Echinochloa , Herbicides , Oxidoreductases , Plant Proteins , Plant Weeds , Pyridazines , Herbicides/pharmacology , Herbicides/chemistry , Pyridazines/pharmacology , Pyridazines/chemistry , Echinochloa/drug effects , Echinochloa/enzymology , Echinochloa/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Plant Proteins/antagonists & inhibitors , Oxidoreductases/genetics , Oxidoreductases/metabolism , Oxidoreductases/antagonists & inhibitors , Oxidoreductases/chemistry , Plant Weeds/drug effects , Plant Weeds/enzymology , Plant Weeds/genetics , Structure-Activity Relationship , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Plant Roots/chemistry , Plant Roots/drug effects , Molecular Structure
4.
Chongqing Medicine ; (36): 276-280,285, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1017477

ABSTRACT

Objective To analyze the health management situation of non-communicable chronic disease(NCD)in Chongqing City and Guizhou Province and its influencing factors.Methods A stratified random sampling method was used to select 16 representative primary medical and health institutions from Chongqing City and Guizhou Province as the research sites,and the data were collected through the combination method of qualitative and quantitative research.Results A total of 760 patients with NCD were surveyed,and the awareness rate,utilization rate and satisfaction rate of the NCD health management program all exceeded 84.2%,while the awareness rate,utilization rate and satisfaction rate of follow-up and categorical intervention were the lowest.The awareness rate of hypertension physical examination in the patients with<60 years old was lower than that in the patients with 60-<70 years old(OR=4.28,95%CI:1.43-12.81)and the pa-tients with ≥70 year sold(OR=3.16,95%CI:1.12-8.91);the utilization rate of diabetes screening in the patients with<60 years-old was lower than that in the patients with ≥70 years old(OR=2.70,95%CI:1.08-6.76)and the awareness rate of hypertension physical examination was lower than that of the patients with 60-<70 years old(OR=4.24,95%CI:1.01-17.75);the awareness rate of hypertension physical ex-amination in the patients in Chongqing City was higher than that in Guizhou Province(OR=0.15,95%CI:0.04-0.54)and the utilization situation was better than that in Guizhou Province(OR=0.13,95%CI:0.05-0.34).Conclusion The overall situation of NCD management services in Chongqing City and Guizhou Province is good,but the service quality of follow-up and classified intervention projects needs to be further improved.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019173

ABSTRACT

Objective To investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP>1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P<0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P<0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1020620

ABSTRACT

Objective:To identify and improve the weakness in different clinical practice teaching hospital,and enhance the quality of practical teaching.Methods:A total of 291 trainees majoring in clinical medicine in grade 2016 in a medical college in Shenyang who practiced in different clinical teaching hospitals and participated in the objective structured clinical examination(OSCE)were enrolled.The OSCE scores was analyzed with one way ANOVA and Kruskal-Wallis statistic methods to identify the weakness in clinical practice teaching and improve the teaching quality.Results:In the standardized patient consultation and physical examination results,the passing rate and average score of H hospital was the lowest.The average score of trainees in H hospital was statistically significant compared to that in A,B,F,G,K,and L hospitals(P<0.01).In terms of skill operation scores,H hospital had the lowest pass rate and average score.The average score of interns in H hospital was statistically significant compared to that in A,D,E,F,G,I,J,K hospitals(P<0.01).In the interpretation of auxiliary examination results,the passing rate and average score of H hospital was the lowest.The average score of interns in A and H hospital was significantly different from that of B and J hospitals(P<0.01).Conclusions:There are great differences in the practice effect of students in different clinical teaching hospitals.Medical colleges and universities should strengthen the management of clinical teaching hospitals to ensure the homogeneity of clinical practice teaching quality.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1039884

ABSTRACT

ObjectiveTo analyze the trends in the disease burden of esophageal cancer attributed to smoking in China from 1990 to 2019. MethodsUsing the Joinpoint 4.9.1.0 software, based on the Global Burden of Disease Study 2019 data, we examined the mortality, Disability-Adjusted Life Years (DALY) data, and death rates of esophageal cancer attributed to smoking in China from 1990 to 2019, along with national population data. The trends in disease burden was described and the age-period-cohort model was employed to analyze the effects of age, period, and cohort on the trends in disease burden due to smoking. ResultsJoinpoint analysis indicated that the age-standardized mortality rate (ASMR) and DALY rate attributable to smoking showed an average annual percent change (AAPC) of -1.42% and -1.72%, respectively. For females, the AAPC values for ASMR and DALY rate were -3.26% and -3.70%, respectively, while for males, these were -1.28% and -1.54%, respectively. The disease burden by age attributable to smoking showed a general declining trend across all age groups in mortality and DALY rates. The disease burden from smoking, measured by age, displayed a consistent downward trend in both mortality and DALY rates across all age groups. The 40-44 age group saw the sharpest decline, with Annual Average Percent Changes (AAPC) of -3.05% for mortality and -3.04% for DALY rates. This was closely followed by the 45-49 age group, which experienced AAPC values of -2.73% and -2.72%, respectively. Analysis using the age-period-cohort model showed that the impact of age on mortality and DALY rates due to smoking initially increases with age before subsequently decreasing. The period effect revealed a general increase in the mortality rate from smoking in China, except for a dip between 2005 and 2010; otherwise, the trend was upward over time. The DALY rate demonstrated variability across different periods. The cohort effect indicated a decrease in both mortality and DALY rates due to smoking as successive birth cohorts progressed. ConclusionsOur study reveals that the disease burden of esophageal cancer attributed to smoking factors exhibits gender differences and shows an overall declining trend over time. Efforts should be intensified to enhance health education for men, particularly focusing on smoking cessation education for smokers aged 35-39, in order to improve the overall level of primary prevention of esophageal cancer.

8.
Int J Biol Macromol ; 242(Pt 2): 124969, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37210050

ABSTRACT

Snake envenoming is both a healthcare and socioeconomic problem for developing countries and underserved communities. In Taiwan, clinical management of Naja atra envenomation is a major challenge, since cobra venom-induced symptoms are usually confused with hemorrhagic snakebites and current antivenom treatments do not effectively prevent venom-induced necrosis for which early surgical debridement should be administered. Identification and validation of biomarkers of cobra envenomation is critical for progress in setting a realistic goal for snakebite management in Taiwan. Previously, cytotoxin (CTX) was determined as one of potential biomarker candidates; however, its ability to discriminate cobra envenoming remains to be verified, especially in clinical practice. In this study, we selected a monoclonal single-chain variable fragment (scFv) and a polyclonal antibody to develop a sandwich enzyme-linked immunosorbent assay (ELISA) for CTX detection, which successfully recognized CTX from N. atra venom over that from other snake species. Using this specific assay, the CTX concentration in envenoming mice was shown to remain consistent in about 150 ng/mL during the 2-hour post-injection period. The measured concentration was highly correlated with the size of local necrosis in mouse dorsal skin, which the correlation coefficient is about 0.988. Furthermore, our ELISA method displayed 100 % of specificity and sensitivity in discriminating cobra envenoming among snakebite victims through CTX detection and the level of CTX in victim plasma was ranged from 5.8 to 253.9 ng/mL. Additionally, patients developed tissue necrosis at plasma CTX concentrations higher than 150 ng/mL. Thus, CTX not only serves as a verified biomarker for discrimination of cobra envenoming but also a potential indicator of severity of local necrosis. In this context, detection of CTX may facilitate reliable identification of envenoming species and improve snakebite management in Taiwan.


Subject(s)
Elapidae , Snake Bites , Animals , Mice , Antivenins/pharmacology , Snake Bites/diagnosis , Snake Bites/therapy , Cytotoxins , Snake Venoms , Elapid Venoms , Enzyme-Linked Immunosorbent Assay/methods , Necrosis
9.
Trop Med Infect Dis ; 8(1)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36668958

ABSTRACT

Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. Deinagkistrodon acutus is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against D. acutus envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to D. acutus venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against D. acutus venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019412

ABSTRACT

Objective:To compare the clinical effects of different approaches of unilateral thyroid lobectomy in the treatment of papillary thyroid microcarcinoma (PTMC) .Methods:From Jun. 2019 to Jun. 2022, 70 patients with PTMC from Thyroid and Breast Surgery Department of Taihe Hospital and Dongfeng General Hospital were selected for prospective study. They were divided into transoral group with 35 cases according to random number table method. Trans-oral endoscopic thyroidectomy (TOET) was adopted in 11 males and 24 females, aging (40.71±5.09) years old, ranging from 23 to 60 years old; 35 cases in the trans-axillary group, using trans-axillary approach Endoscopic thyroidectomy by areola approach (ETAA) including 13 males and 22 females, aging (40.25±5.06) years old, ranging from 24 to 59 years old. Perioperative indicators, inflammatory factors, and stress indicators were recorded in the two groups. The level and complications were followed up for 3 months to evaluate the aesthetics of surgical incisions. The comparison of measurement data between groups was performed by independent t test, and the comparison of count data was conducted by χ2 test. Results:The number of lymph nodes dissected and intraoperative blood loss in the oral cavity group were significantly better than those in the axillary group [ (8.71±0.93) vs (6.85±0.82), (23.05±3.51) ml vs (26.14±3.96) ml] ( t=8.88, 3.46, P<0.05) ; The first day after operation, serum norepinephrine (NE) and cortisol (Cor) in the oral cavity group were significantly lower than those in the axillary group [ (275.31±30.41) ng/L vs (300.22±33.25) ng/L, (180.25±19.75) nmol/L vs (205.36±22.41) nmol/L] ( t=3.27, 4.97, P<0.05) ; The first day after operation, the levels of serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the oral cavity group were significantly lower than those in the axillary group [ (7.05±0.86) mg/L vs (8.74±1.02) mg/L, (4.33±0.62) pg/L vs (6.45±0.81) pg/L] ( t=7.49, 12.30, P<0.05) ; there was no significant difference in the incidence of complications between the groups ( P>0.05) ; Three months postoperatively, the aesthetics of the incision in the oral cavity group (94.29%) was significantly higher than that in the axillary group (77.14%) ( χ2=4.20, P<0.05) . Conclusion:When unilateral thyroid lobectomy is performed for papillary thyroid microcarcinoma, the transoral vestibular approach is less invasive than the transaxillary approach, and the effect of lymph node dissection is better, which is beneficial to reduce the surgical stress response of patients, and the aesthetics of the surgical incision are higher.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-998752

ABSTRACT

Background Occupational pneumoconiosis is the most common occupational disease in Qinghai Province and China. From the perspective of public health, it is important to assess the disease burden using disability-adjusted life years (DALY) and economic losses. Objective To evaluate the disease burden of occupational pneumoconiosis in Qinghai Province, and to provide a basis for the formulation and implementation of relevant prevention and control strategies. Methods Based on the registered data, a database of occupational pneumoconiosis cases confirmed and reported in Qinghai Province was established. The survival status and death dateof occupational pneumoconiosis patients from 2015 to 2019 were confirmed by on-site visit, telephone survey, matching search of Death Information Registration and Management System, and consulting other departments. The life loss due to occupational pneumoconiosis from 2015 to 2019 was assessed using DALY as an indicator and data from the Global Burden of Disease 2019 (GBD 2019) study. Inpatients with officially diagnosed occupational pneumoconiosis from a hospital in Qinghai Province in 2019 were selected as study subjects, the direct economic loss was evaluated with hospitalization expenses, and the indirect economic loss due to occupational pneumoconiosis in Qinghai Province in 2019 was calculated by human capital approach. Results From 2015 to 2019, 505 new cases of occupational pneumoconiosis were reported in Qinghai Province, and there were 348 death cases. Prevalent cases and years lost due to disability (YLD) due to occupational pneumoconiosis were increased, while DALY and years of life lost (YLL) due to occupational pneumoconiosis decreased firstly and then increased. In each year, there were 87% or more of the DALY, YLL, or YLD attributed to silicosis and coal workers' pneumoconiosis. In 2019, the occupational pneumoconiosis-associated DALY was 2173.55 person years. The total hospitalization expense incurred by 42 inpatients with occupational pneumoconiosis was 1256345.19 yuan. The total hospitalization expense and average daily cost of the inpatients with stageⅡand Ⅲ pneumoconiosis were higher than that of the inpatients with stageⅠ (P<0.05), and the hospitalization expense was higher in the ≥60 years age group than in the <60 years age group (P<0.05). In 2019, the indirect economic burden incurred by occupational pneumoconiosis in Qinghai Province was 44108581.65 yuan, and accounted for 0.15‰ of the gross domestic product (GDP) of the province. Conclusion The disease burden associated with occupational pneumoconiosis in Qinghai Province are outstanding. Silicosis and coal workers' pneumoconiosis are the key contributors. Targeted intervention measures including dust hazard control, enterprise management, follow-up and rehabilitation management of pneumoconiosis should be taken to prevent and control the occurrence and progression of pneumoconiosis and alleviate disease burden of pneumoconiosis.

12.
Toxins (Basel) ; 14(7)2022 07 04.
Article in English | MEDLINE | ID: mdl-35878197

ABSTRACT

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.


Subject(s)
Naja naja , Single-Chain Antibodies , Animals , Antivenins/pharmacology , Chickens , Cytotoxins , Elapid Venoms/toxicity , Elapidae , Female , Myoblasts , Necrosis , Single-Chain Antibodies/pharmacology
13.
J Agric Food Chem ; 70(24): 7400-7411, 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35687877

ABSTRACT

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for the development of new herbicides. HPPD inhibitors can hinder photosynthesis and induce weed death with bleaching symptoms. To explore the novel skeleton of HPPD inhibitors, a series of novel pyrazole amide derivatives were synthesized and evaluated for their inhibitory effects on Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activities. Some compounds had excellent inhibitory activities against AtHPPD. Among them, compound B5 displayed top-rank inhibitory activity against AtHPPD with an IC50 value of 0.04 µM, which was obviously superior to that of topramezone (IC50 value of 0.11 µM). Furthermore, compounds B2 and B7 had 100% herbicidal activities in Petri dish assays against Portulaca oleracea and Amaranthus tricolor at 100 µg/mL. In particular, compound B7 not only possessed strong AtHPPD inhibitory activity but also exhibited significant preemergence herbicidal activity. However, compound B7 was completely harmless to soybean, cotton, and wheat. In addition, the molecular docking and microscale thermophoresis measurement experiment verified that compounds can bind well with AtHPPD via π-π interactions. The present work provides a new approach for the rational design of more effective HPPD inhibitors, and pyrazole amides could be used as useful substructures for the development of new HPPD inhibitors and preemergence herbicidal agents.


Subject(s)
4-Hydroxyphenylpyruvate Dioxygenase , Arabidopsis , Herbicides , Amides/pharmacology , Arabidopsis/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Herbicides/chemistry , Herbicides/pharmacology , Molecular Docking Simulation , Molecular Structure , Pyrazoles/chemistry , Pyrazoles/pharmacology , Structure-Activity Relationship
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-955535

ABSTRACT

Five universities with health policy and management ranked top level worldwide, including Harvard University, John Hopkins University, Stanford University, University of North Carolina at Chapel Hill and National University of Singapore were selected in our study. From above universities, we found that the curriculum of PHD students was focused on research concentration, methodology courses, and numerous elective courses. Hence, in China, the curriculum of PHD students should be improved with emphasis on course studying, management courses and highlighting curriculum content according to research area to enhance the quality of doctoral education.

15.
Chinese Journal of Cardiology ; (12): 132-136, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-935116

ABSTRACT

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.


Subject(s)
Aged , Aged, 80 and over , Humans , Male , Anticoagulants , Aortic Valve , Aortic Valve Stenosis/surgery , Atrial Fibrillation/drug therapy , Follow-Up Studies , Retrospective Studies , Risk Factors , Transcatheter Aortic Valve Replacement , Treatment Outcome
16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-928352

ABSTRACT

OBJECTIVE@#To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region.@*METHODS@#Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves.@*RESULTS@#4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively.@*CONCLUSION@#HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.


Subject(s)
Humans , Genotype , Hemoglobin A2/genetics , Heterozygote , Mass Screening , Mutation , alpha-Thalassemia , beta-Thalassemia/genetics
17.
Chinese Medical Journal ; (24): 2556-2563, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-921163

ABSTRACT

BACKGROUND@#Ankylosing spondylitis (AS) is a common chronic progressive rheumatic disease. The aim of this study was to explore factors influencing abnormal bone mineral density (BMD) in young and middle-aged patients with AS.@*METHODS@#From July 2014 to August 2018, hospitalized patients with AS and health examinees in the health examination center of our clinics, ranging in age from 20 to 50 years, were monitored. The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption. The BMDs of AS patients were compared with respect to age, course of disease, iritis, smoking habits, sex, height, weight, body mass index (BMI), medication use, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet volume, platelet count, uric acid (UA), alkaline phosphatase (AKP), and calcium ion levels. Single-nucleotide polymorphisms (SNPs) related to BMD were screened using genome-wide association analysis.@*RESULTS@#There was no statistical difference in the proportion of abnormal bone masses between the different body parts. The BMD of all bones in AS patients was lower than that in healthy controls (P < 0.05). Additionally, BMD was correlated with serum calcium and CRP in AS patients (P < 0.05), but not with age, platelet volume, platelet count, ESR, UA, AKP, height, weight, and BMI. The incidence of abnormal bone mass in AS patients was correlated with sex (P < 0.05), but not with medication use, iritis, or smoking. BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease, but BMD of the femoral neck correlated linearly with the course of the disease (P < 0.05). BMD was correlated with multiple SNPs in patients with AS. Lumbar BMD was correlated with rs7025373 and rs7848078. Femoral head BMD was correlated with 3:102157365, 3:102157417, rs1252202, rs1681355, rs3891857, rs7842614, and rs9870734, suggesting that genetic factors play a role in BMD in patients with AS.@*CONCLUSIONS@#The proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age. The factors related to BMD in patients with AS are gender, CRP, and blood calcium. The BMD of the femoral neck of AS patients decreases with the course of the disease, but BMD of the lumbar spine is not related to the course of the disease. BMD in AS patients is associated with multiple SNPs.


Subject(s)
Adult , Humans , Middle Aged , Young Adult , Absorptiometry, Photon , Bone Density , Femur Neck , Genome-Wide Association Study , Lumbar Vertebrae , Spondylitis, Ankylosing/genetics
18.
Chinese Journal of Cardiology ; (12): 121-127, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-941247

ABSTRACT

Objective: To evaluate the five-year safety and efficacy of the second generation biodegradable polymer sirolimus-eluting stent (EXCROSSAL) in treating patients with de novo coronary artery diseases. Methods: Patients with coronary artery disease (CAD)who were implanted with EXTROSSAL stents in CREDIT Ⅱ and CREDIT Ⅲ study were included. CREDIT Ⅱ was a randomized trial, and CREDIT Ⅲ was a single-arm study. From November 2013 to December 2014, 833 CAD patients with de novo coronary lesions implanted with EXTROSSAL stents were selected from 33 centers in China. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularization. Secondary endpoints was patient-oriented composite endpoint (PoCE), including all-cause death, all myocardial infarction, or any revascularization within 5 years post stenting and stent thrombosis according to Academic Research Consortium's (ARC) definition. Kaplan Meier method was used to calculate the incidence of TLF and PoCE within 5 years after operation. Univariate Cox regression analysis was used to analyze the impacts of diabetes, small vessel disease (vessel diameter ≤ 2.74 mm), lesion length ≥ 16.7 mm and multivessel disease on the incidence of TLF within 5 years after operation. Results: A total of 833 patients were included in this study including 579 males (69.5%), the age was (59.3±9.1) years. And 832 (99.9%) patients completed 5-year clinical follow-up. The incidence of TLF and PoCE in the 5-year follow-up were 10.6%(86/811) and 15.5%(126/811), respectively. Stent thrombosis occurred in 1.0%(8/811) of patients. Univariate Cox regression analysis showed that vessel diameter ≤ 2.74 mm (HR=3.20,95%CI 1.90-5.39,P<0.001), lesion length ≥ 16.7 mm (HR=1.88,95%CI 1.18-2.99,P=0.007) and multivessel disease (HR=2.44,95%CI 1.60-3.72,P<0.001) were related factors of TLF within 5 years after operation. Conclusion: EXCROSSAL stent is effective and safe in treating CAD patients with de novo coronary lesions, with low incidence of TLF and PoCE within 5 years after operation.


Subject(s)
Aged , Humans , Male , Middle Aged , Cardiovascular Agents , China , Coronary Artery Disease/surgery , Drug-Eluting Stents , Percutaneous Coronary Intervention , Polymers , Risk Factors , Sirolimus/therapeutic use , Time Factors , Treatment Outcome
19.
Chinese Journal of Cardiology ; (12): 764-769, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-941350

ABSTRACT

Objective: To observe the incidence of perioperative severe complications in aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVR), and to explore the influence of the accumulated experience of the operators on the incidence of complications. Methods: This is a single-center retrospective study. Patients with AS who underwent TAVR from May 2016 to November 2020 in General Hospital of Northern Theater Command were included. The occurrence of severe complications during perioperative period was recorded. Severe complications included all-cause death, surgical transfer to thoracotomy, coronary artery occlusion, peripheral vascular approach complications, severe cerebrovascular events, moderate or above perivalvular leakage, valve displacement (implanted valve middle valve), pacemaker implantation, etc. In order to observe the influence of the accumulated experience of the operators on the occurrence of postoperative complications, the complications in each stage of the patients were counted and the bar chart was drawn with interval of every 30 patients. Results: A total of 119 patients were included, including 64 males and 55 females, the mean age was (73.9±6.9) years. The valve implantation was unsuccessful in 3 out of 119 patients (2.5%). There were 39 cases of severe complications during perioperative period, including 1 death (0.8%), 2 cases of thoracotomy (1.7%), 2 cases of coronary artery occlusion (1.7%), 8 cases of peripheral vascular approach complications (6.7%), and 1 case of new severe cerebrovascular event (0.8%), 3 cases of moderate or higher perivalvular leakage (2.5%), 8 cases of valve displacement leads to midvalvular implantation (6.7%), 14 cases of permanent pacemaker implantation due to new atrioventricular block (11.8%). The bar chart showed that the incidence of permanent pacemaker implantation and in-valve implantation did not significantly decrease with the accumulation of experience, while the incidence of other complications showed a decreasing trend after 30 cases. Conclusions: Most serious complications occurred in the early stage of TAVR in our center. The incidence of all cause death, coronary artery occlusion and peripheral vascular approach complications in the perioperative period post TAVR could be reduced in the TAVR center in the learning stage through the accumulation of procedure-related experience, but the incidence of pacemaker placement and the implanted valve within the valve dose not significantly decrease over time.

20.
Chinese Medical Journal ; (24): 1720-1725, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-887614

ABSTRACT

BACKGROUND@#Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal.@*METHODS@#Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued  0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P  0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups.@*CONCLUSIONS@#Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.


Subject(s)
Aged , Humans , Case-Control Studies , Clopidogrel/therapeutic use , Hip Fractures/surgery , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Ticlopidine/adverse effects
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