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1.
Article in English | WPRIM | ID: wpr-928651

ABSTRACT

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.


Subject(s)
Beijing/epidemiology , Diabetes Mellitus/epidemiology , Female , Hospitalization , Humans , Male , Memory, Short-Term , Neural Networks, Computer
2.
Asian Journal of Andrology ; (6): 213-218, 2022.
Article in English | WPRIM | ID: wpr-928528

ABSTRACT

Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.


Subject(s)
Animals , Cytokines/metabolism , Disease Models, Animal , Ejaculation/physiology , Interleukin-1beta/metabolism , Male , N-Methylaspartate/metabolism , Prostate/metabolism , Prostatitis/metabolism , Rats , Receptors, N-Methyl-D-Aspartate/metabolism
3.
Article in Chinese | WPRIM | ID: wpr-928083

ABSTRACT

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 μm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.


Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal/chemistry , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry
4.
Article in Chinese | WPRIM | ID: wpr-927923

ABSTRACT

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.


Subject(s)
Animals , Bile Acids and Salts , Chromatography, Liquid , Drugs, Chinese Herbal , Ileum , Liver , Mice , Sleep Initiation and Maintenance Disorders/drug therapy , Tandem Mass Spectrometry
5.
Article in Chinese | WPRIM | ID: wpr-927847

ABSTRACT

Objective To investigate the correlations of diffusion weighted imaging (DWI) with pathological grading,typing and clinical staging of cervical adenocarcinoma. Methods The data of 95 patients with cervical adenocarcinoma from May 2011 to February 2018 in Cancer Hospital Chinese Academy of Medical Sciences were collected for retrospective analysis.Before treatment,conventional MRI and DWI (b=0,800 s/mm2) were performed,and the apparent diffusion coefficient (ADC) value of cervical adenocarcinoma was measured.The ADC values were compared among different pathological grades,types,and clinical stages. Results The mean ADC value was (1.00±0.25)×10-3 mm2/s in the poorly differentiation group,(1.09±0.25)×10-3 mm2/s in the moderately differentiation group,and (1.22±0.20)×10-3 mm2/s in the well differentiation group,which showed significant difference between the poorly and well differentiation groups (P=0.002).The mean ADC values were (1.04±0.24) ×10-3 mm2/s and (1.21±0.26)×10-3 mm2/s in the endocervical adenocarcinoma (usual type) group and mucinous carcinoma group,respectively,which showed significant difference (P=0.005). Conclusions The worse differentiation of cervical adenocarcinoma corresponded to the lower ADC value.The ADC value of mucinous carcinoma was higher than that of endocervical adenocarcinoma (usual type).


Subject(s)
Adenocarcinoma/pathology , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Retrospective Studies , Uterine Cervical Neoplasms/diagnostic imaging
6.
Journal of Preventive Medicine ; (12): 541-546, 2022.
Article in Chinese | WPRIM | ID: wpr-927236

ABSTRACT

Objective@#To estimate the burden of disease (BOD) attributable to main risk factors of chronic diseases in Zhejiang Province in 2017, so as to provide the evidence for formulating the control strategy for chronic diseases and reducing BOD.@*Methods@#The results of the Global Burden of Disease Study 2017 ( GBD 2017 ) were extracted to evaluate years of life lost due to premature mortality ( YLL ), years lived with disability ( YLD ) and disability-adjusted life years ( DALY ). The gender- and age-specific BOD attributable to main risk factors of chronic diseases, including the environment, metabolism and behaviors, in Zhejiang Province in 2017 was estimated and compared with those in 1990.@*Results@#High DALY rates of chronic diseases were estimated attributable to tobacco use ( 2 807.08/105 ), unreasonable diet ( 2 724.72/105 ) and hypertension ( 1 878.69/105 ) in Zhejiang Province in 2017, and high DALY rates of chronic diseases were estimated in men attributable to tobacco use ( 4 764.77/105 ), unreasonable diet ( 3 297.00/105 ) and hypertension ( 2 076.92/105 ), while high DALY rates of chronic diseases were estimated in women attributable to unreasonable diet ( 2 117.16/105 ), hypertension ( 1 668.24/105 ) and hyperglycemia ( 1 100.53/105 ), respectively. Among individuals at ages of 15 to 49 years, high DALY rates of chronic diseases were estimated attributable to unreasonable diet ( 759.29/105 ), drug abuse ( 611.71/105 ) and tobacco use ( 605.37/105 ); among individuals at ages of 50 to 69 years, high DALY rates of chronic diseases were estimated attributable to tobacco use ( 5 528.37/105 ), unreasonable diet ( 4 628.18/105 ) and hypertension ( 2 757.78/105 ); and among individuals at ages of 70 years and older, high DALY rates of chronic diseases were estimated attributable to unreasonable diet ( 16 370.09/105 ), tobacco use ( 15 551.40/105 ) and hypertension ( 14 408.63/105 ). As compared to those in 1990, the DALY rates of chronic diseases attributable to high body mass index, alcohol use, hyperglycemia, high low-density lipoprotein cholesterol and drug abuse increased by 108.23%, 48.59%, 23.17%, 17.64% and 6.06%, and the DALY rates of chronic diseases attributable to air pollution, occupational risks, unreasonable diet and impaired renal function reduced by 51.11%, 44.81%, 22.49% and 19.83%, and no significant alterations were detected in DALY rates of chronic diseases attributable to tobacco use or hypertension in 2017.@*Conclusions@#There was a high BOD of chronic diseases attributable to tobacco use, unreasonable diet and hypertension in Zhejiang Province in 2017, and the BOD of chronic diseases attributable to high body mass index, alcohol use and hyperglycemia appeared a tendency towards a rise in Zhejiang Province in 2017 relative to in 1990.

7.
Yonsei Medical Journal ; : 282-291, 2022.
Article in English | WPRIM | ID: wpr-927152

ABSTRACT

Purpose@#As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported that microRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5p has been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatory mechanism of miR-322-5p in vascular dementia. @*Materials and Methods@#In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce the model of chronic brain hypoperfusion. @*Results@#MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VO rats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpression of TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/Rtreated neurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. @*Conclusion@#Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. This discovery may provide a potential therapeutic target for dementia.

8.
Acta Pharmaceutica Sinica ; (12): 1312-1321, 2022.
Article in Chinese | WPRIM | ID: wpr-924761

ABSTRACT

The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.

9.
Acta Pharmaceutica Sinica ; (12): 1516-1525, 2022.
Article in Chinese | WPRIM | ID: wpr-924752

ABSTRACT

italic>Glycyrrhiza eurycarpa P.C.Li is a medicinal plant resource and is often mixed with traditional licorice herbs. We sequenced the chloroplast genome of Glycyrrhiza eurycarpa P.C.Li using Illumina high-throughput sequencing technology, and physical mapping and genomic characterization was carried out. Comparative genomic analysis was performed with Glycyrrhiza uralensis Fisch, Glycyrrhiza inflata Bat and Glycyrrhiza glabra L. The Glycyrrhiza eurycarpa P.C.Li chloroplast genome was 127 864 bp long with 34.25% GC content, consisting of a large single copy and a small single copy. The genome was missing the inverted repeat (IR) region. A total of 110 genes were annotated, including 76 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The 301 SSRs, rich in A-T repeats, were detected by MISA. The Glycyrrhiza eurycarpa P.C.Li chloroplast genome showed weak codon preference, and the codons were biased to use A and T bases. Three specific gene fragments of Glycyrrhiza eurycarpa P.C.Li were characterized by homology comparison. Based on Pi analysis, six new high mutation regions (psbZ-psbC, trnC-GCA-rpoB, trnR-UCU-trnG-UCC, ycf2, trnN-GUU-ycf1, ndhA) of medicinal licorice species were determined. The results of phylogenetic analysis indicate that Glycyrrhiza eurycarpa P.C.Li from Xinjiang is an interspecific hybrid taxon closely related to the three medicinal licorice species, and Glycyrrhiza inflata Bat, which is distributed in the same domain, is its male parent. Based on this study, the taxonomic identification, herb-specific DNA fingerprint development, genetic diversity, and molecular plant breeding of medicinal plants of the genus Glycyrrhiza can be established.

10.
Article in Chinese | WPRIM | ID: wpr-924646

ABSTRACT

ObjectiveTo evaluate the effects of transcranial direct current stimulation (tDCS) on post-stroke aphasia (PSA). MethodsLiteratures about tDCS for PSA were retrieved from PubMed, Web of Science, Cochrane library, Embase CNKI and Wanfang Data, until December, 2021. The contents of the author, publication time, subjects, intervention methods and time, main outcome indicators and conclusions were extracted. ResultsA total of 1 026 articles were returned and 45 articles were finally included. The publication time was from 2010 to 2021. The subjects of the study were patients with PSA. The main outcome indicators were the various speech scales and their sub-items. For most of the trials, scores of the scales were better in the experimental groups than in the control groups after treatment, and a few found little improvement in Boston Diagnostic Aphasia Examination, or only improved in complex language tasks. tDCS can improve the repetition, naming, spelling and verbal fluency of PSA patients, which might relate with electrode placement, current magnitude, duration, intensity and left cortical integrity. ConclusiontDCS is effective on different language sub-items of PSA, and various with the program of tDCS.

11.
Organ Transplantation ; (6): 356-2022.
Article in Chinese | WPRIM | ID: wpr-923582

ABSTRACT

Objective To investigate the exposure difference of different dosage forms of mycophenolic acid (MPA) between children aged ≤12 and > 12 years old after kidney transplantation. Methods Clinical data of 73 children undergoing kidney transplantation from donation after cardiac death (DCD) were retrospectively analyzed. Postoperative immunosuppressive regimen was MPA+ tacrolimus+glucocorticoid. According to different dosage forms of MPA, all recipients were divided into group A (n=37, mycophenolate mofetil capsules), group B (n=28, enteric-coated mycophenolate sodium) and group C (n=8, mycophenolate mofetil dispersible tablets). All children were divided into ≤12 and > 12 years old groups according to the age of kidney transplantation. The daily dosage of different dosage forms was calculated. The blood concentration (C) of MPA and the area under the curve (AUC) were detected by enzyme-multiplied immunoassay technique. The MPA blood concentration was statistically compared between two age groups at different time points. The recovery of renal function and postoperative complications were assessed. Results No significant differences were observed in the dosage and blood concentration of drug at different time points among groups A, B and C (all P > 0.05). The MPA-C4 h and AUC in the ≤12 years old group were significantly higher than those in the > 12 years old group (both P < 0.05). In group B, the MPA-C4 h of children aged ≤12 years old was significantly higher compared with that in those aged > 12 years old (P=0.016). The MPA-C4 h of children aged ≤12 years old in group B was higher than those in group A and group C, but the differences were not statistically significant (P=0.080). There was no significant difference in the incidence of acute rejection and infection among three groups (both P > 0.05). Conclusions Children of different ages who are given with different dosage forms of MPA after kidney transplantation obtain different exposure rates. The exposure rate of kidney transplant recipients aged ≤12 years old tends to be higher than that of their counterparts aged > 12 years old, mainly seen in the recipients treated with enteric-coated mycophenolate sodium. Therefore, it is necessary to monitor the exposure level of MPA, which provides significant guidance for adjusting the drug dosage of different dosage forms.

12.
China Pharmacy ; (12): 879-884, 2022.
Article in Chinese | WPRIM | ID: wpr-923197

ABSTRACT

OBJECTIVE To systematically evaluate the efficacy and safety of fondaparinux versus low molecular weight heparin(nadroparin,enoxaparin)in the treatment of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS The computer searched PubMed ,Medline,Embase,EBSCO,CNKI,Wanfang medical network ,VIP Chinese Journal Full-text Database and relevant clinical trial registration network for the clinical retrospective cohort study (RCS)of fondaparinux (as trial group)and low molecular weight heparin (natroparin,enoxaparin)(as control group )in the treatment of NSTE-ACS. The retrieval time limit was from the establishment of the database to August 2021. Newcastle Ottawa scale (NOS)was used to evaluate the quality of literature. Outcome indicators included primary efficacy indicators (incidence of acute myocardial infarction and recurrent angina pectoris during hospitalization ),secondary efficacy indicators [revascularization of target vessels during 话:0835-2862024。E-mail:xiexingxing07@163.com hospitalization, prothrombin time (PT), activated partial thromboplastin time (APTT)],safety indicators (incidence of serious cardiovascular events ,severe bleeding ,slight bleeding and severe puncture site co mplications during hospitalization ),combined endpoint indicators (30 and 180 days combined endpoint). RevMan 5.3 software was used for Meta-analysis of each effect index. RESULTS Finally,17 RCS articles were included,involving 4 946 patients with NSTE-ACS ,including 2 507 in the trial group and 2 439 in the control group.The results of NOS literature quality evaluation showed that there were 8 high-quality studies ,accounting for 47.06% . The results of Meta-analysis showed that there was no significant difference in the incidence of acute myocardial infarction ,recurrent angina pectoris,revascularization of target vessels ,PT and serious cardiovascular events between 2 groups (P>0.05);there was significant difference in the APTT (MD=1.34,95%CI of 0.22-2.45,P<0.05),the incidence of severe bleeding (RR=0.47, 95%CI of 0.30-0.74,P<0.05),the incidence of slight bleeding (RR=0.48,95%CI of 0.32-0.71,P<0.05),the incidence of severe puncture site complications (RR=0.48,95%CI of 0.25-0.95,P<0.05),30 day combined endpoint (RR=0.57,95%CI of 0.46-0.72,P<0.05),180 days combined endpoint (RR=0.73,95%CI of 0.54-0.98,P<0.05). CONCLUSIONS Fondaparinux in the treatment of NSTE-ACS in China has the same efficacy as low molecular weight heparin (nadroparin,enoxaparin),and has more obvious advantages in drug safety such as bleeding ,severe puncture site complications.

13.
China Pharmacy ; (12): 758-763, 2022.
Article in Chinese | WPRIM | ID: wpr-923015

ABSTRACT

The re gulators of renin-angiotensin system (RAS) include renin inhibitors ,angiotensin converting enzyme inhibitors,angiotensin Ⅱ receptor blockers ,angiotensin Ⅱ receptor agonists and angiotensin 1-7. This paper summarizes and analyzes the adjuvant effects of RAS regulators on antitumor drugs by searching the literature published from January 1992 to June 2021. The regulators of RAS can reduce the cardiotoxicity ,hematological toxicity and peripheral neurotoxicity of antitumor drugs , and has renal protective effect ;the regulators of RAS combined with other chemotherapy drugs show favorable effects on promoting chemotherapeutic drugs delivery ,improving anti-angiogenesis and bypass activation of targeted drugs ,enhancing tumor immune response of immune checkpoint inhibitors ,so as to improve therapeutic efficacy of antitumor drugs. The combination of RAS regulators with antitumor drugs is expected to reduce the side effects of antitumor drugs ,enhance its efficacy and improve the prognosis of patients.

14.
Acta Pharmaceutica Sinica ; (12): 576-592, 2022.
Article in Chinese | WPRIM | ID: wpr-922887

ABSTRACT

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

15.
Article in Chinese | WPRIM | ID: wpr-936291

ABSTRACT

OBJECTIVE@#To explore the interaction between reactive oxygen species (ROS) and ferroptosis in methylglyoxalinduced injury of mouse embryonic osteoblasts (MC3T3-E1 cells).@*METHODS@#MC3T3-E1 cells were treated with methylglyoxal to establish a cell model of diabetic osteoporosis. CCK-8 assay was used to detect the viability of MC3T3-E1 cells. Rhodamine 123 staining followed by photofluorography was used to examine mitochondrial membrane potential (MMP). The intracellular ROS level was detected by 2', 7'-dichlorodihydrofluorescein diacetate staining with photofluorograph. Alkaline phosphatase (ALP) activity in the cells was detected using an ALP kit, the number of mineralized nodules was determined with alizarin red S staining, and the level of iron ions was detected using a detection kit. The expression level of glutathione peroxidase 4 (GPX4, a marker protein that inhibits ferroptosis) in the osteoblasts was determined using Western blotting.@*RESULTS@#Treatment of MC3T3-E1 cells with 0.6 mmol/L methylglyoxal for 24 h significantly inhibited the expression level of GPX4 (P < 0.001), increased intracellular iron ion concentration, decreased the cell viability, increased the loss of MMP and intracellular ROS level, decreased both ALP activity and the number of mineralized nodules in the cells (P < 0.001). Co-treatment of MC3T3-E1 cells with 2 mmol/L N-acetylcysteine (NAC, a ROS scavenger) and methylglyoxal significantly increased the expression level of GPX4 (P < 0.01); co-treatment with 4 mmo/L FER-1 (a ferroptosis inhibitor) and methylglyoxal obviously decreased the intracellular ROS level (P < 0.001). Co-treatment of the cells either with NAC and methylglyoxal or with FER-1 and methylglyoxal attenuated methylglyoxal-induced injuries in the osteoblasts (P < 0.001).@*CONCLUSION@#The interaction between ROS and ferroptosis pathway plays an important role in methylglyoxal-induced injury of mouse embryonic osteoblasts.


Subject(s)
Animals , Cell Survival , Ferroptosis , Mice , Osteoblasts , Pyruvaldehyde/metabolism , Reactive Oxygen Species/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-936152

ABSTRACT

OBJECTIVE@#To compare the clinical effect of microsurgery and endovascular embolization in the treatment of spinal dural arteriovenous fistula (SDAVF) by meta-analysis.@*METHODS@#A systematic review was performed to retrieve all relevant literature about surgical treatment or endovascular embolization of SDAVF up to December 2019 through PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials Results, CNKI, Wanfang Data, and SinoMed. The Chinese and English key words included: "SDAVF", "spinal dural arteriovenous fistula", "spinal AVM", "spinal vascular malformation and treatment". The included studies were evaluated using the Newcastle-Ottawa scale. The early failure rate, long-term recurrence, neurological recovery, and complications were evaluated and the clinical effects of the two methods in the treatment of SDAVF were compared by using RevMan 5.3 software. And a further subgroup analysis of the therapeutic effect of endovascular embolization with different embolic agents was conducted.@*RESULTS@#A total of 46 studies involving 1 958 cases of SDAVF were included, in which 935 cases were treated by microsurgery and 1 023 cases were treated by endovascular embolization. The funnel plot demonstrated that there was no publication bias. The results of meta-analysis showed that the incidence of early surgical failure was lower than that of endovascular embolization (OR=0.20, 95%CI: 0.13-0.30, P < 0.05), and the long-term recurrence was also lower than that of endovascular embolization (OR=0.36, 95%CI: 0.22-0.58, P < 0.05). The improvement of neurological function in the surgical patients is significantly higher than that in the patients treated with endovascular embolization (OR=2.86, 95%CI: 1.36-5.99, P < 0.05). There was no significant difference in the occurrence of complications in these two groups (OR=1.52, 95%CI: 0.88-2.64, P=0.14). In the cases of endovascular embolization, the risk of treatment failure or recurrence was higher with Onyx glue than with n-butyl 2-cyanoacrylate (NBCA), and the difference was statistically significant (OR=4.70, 95%CI: 1.55-14.28, P < 0.05).@*CONCLUSION@#Although the treatment of dural arteriovenous fistulas by intravascular embolization has been widely used, the clinical effect of microsurgery is still better than that of endovascular embolization. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of endovascular treatment in SDAVF patients.


Subject(s)
Central Nervous System Vascular Malformations/surgery , Embolization, Therapeutic/methods , Enbucrilate/therapeutic use , Endovascular Procedures/methods , Humans , Microsurgery/methods , Retrospective Studies , Treatment Outcome
17.
Article in Chinese | WPRIM | ID: wpr-936145

ABSTRACT

OBJECTIVE@#To investigate the consistency of cytomegalovirus deoxyribo nucleic acid (CMV-DNA) and immunoglobulin M (IgM) antibody detections in patients with different clinical characteristics and their guiding value for clinical practice.@*METHODS@#From December 2014 to November 2019, a total of 507 patients who were detected with both CMV-IgM and CMV-DNA were collected in Peking University International Hospital. Their general information, such as gender, age and clinical data, including the patient's diagnosis, medication, and outcome were also collected. The groups were stratified according to whether CMV-DNA was negative or positive, CMV-IgM was negative or positive, age, gender, and whether they received immunosuppressive therapy or not. The Pearson Chi-square test or Fisher's exact test was used for comparison of the rates between the groups. P < 0.05 means the difference is statisti-cally significant.@*RESULTS@#Of the 507 patients submitted for examination, 55 (10.85%) were positive for CMV-DNA, 74 (14.60%) were positive for CMV-IgM, and 20 (3.94%) were positive for both CMV-DNA and CMV-IgM. Of the 55 patients with CMV-DNA positive, 37 were male, accounting for 67.27%. In addition, 25 patients were older than 60 years, accounting for 45.45% and 33 patients received immunosuppressive therapy, accounting for 60%. The rates were higher than that of CMV-DNA negative group, 47.35% (P=0.005), 68.14% (P=0.043), 46.02% (P=0.050), respectively. Of the patients with both CMV-DNA and IgM positive, 45% received immunosuppressive threapy, which was lower than that of CMV-DNA positive but IgM negative patients (68.57%, P=0.086), and also lower than CMV-DNA negative but IgM positive patients (68.52%, P=0.064). In the patients with both CMV-DNA and IgM positive, 91.67% showed remission after receiving ganciclovir, whereas in the patients with CMV-DNA positive but IgM negative, the rate was only 60% (P=0.067).@*CONCLUSION@#CMV-IgM antibody detection is affected by age, gender, and immune status. It is not recommended to use CMV-IgM alone to determine CMV infection in patients with immunosuppressive status and those older than 60 years. CMV-DNA and CMV-IgM combined detection may help to predict patients' immune status and outcomes of antiviral therapy.


Subject(s)
Antibodies, Viral , Cytomegalovirus/genetics , Cytomegalovirus Infections/drug therapy , DNA , Female , Humans , Immunoglobulin M , Immunosuppressive Agents/therapeutic use , Male , Nucleic Acids
18.
Protein & Cell ; (12): 180-202, 2022.
Article in English | WPRIM | ID: wpr-929176

ABSTRACT

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.


Subject(s)
Animals , Caenorhabditis elegans/metabolism , Cation Transport Proteins/genetics , Homeostasis , Mitochondria/metabolism , Zinc/metabolism
19.
Neuroscience Bulletin ; (6): 459-473, 2022.
Article in English | WPRIM | ID: wpr-929103

ABSTRACT

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.


Subject(s)
Animals , Blinking , Cerebellar Nuclei/physiology , Cerebellum , Mice , Neurons/physiology , Thalamus
20.
Article in Chinese | WPRIM | ID: wpr-936104

ABSTRACT

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.


Subject(s)
Anastomosis, Surgical/methods , Esophagogastric Junction/surgery , Gastrectomy/methods , Gastroesophageal Reflux/surgery , Humans , Quality of Life , Stomach Neoplasms/surgery
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