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italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H2O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS2 data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.
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AIM: To explore the correlation between neonatal retinal hemorrhage(RH)and changes in umbilical artery blood gas analysis.METHODS: A total of 312 full-term neonates born in our obstetrics department from January 2019 to December 2021 were selected as the study subjects. According to the RetCam III fundus examination results, 245 neonates who did not experience RH were included in the control group, while 67 cases with RH were found to be included in the RH group. In addition, neonates were grouped into I degree group(n=20), II degree group(n=29), and III degree group(n=18)based on the degree of RH. General clinical data and umbilical artery blood gas analysis indicators between the RH group and the control group were compared; the levels of umbilical artery blood gas analysis indicators in neonates with different degrees of RH, the relationship between pH and RH degree, and the influencing factors of neonatal RH were analyzed.RESULTS: There was no obvious difference in maternal age, average gestational week, fetal gender, parity, gestational diabetes, fetal birth weight, and amniotic fluid between the RH group and the control group(all P>0.05), while there were obvious differences in delivery methods, gestational hypertension, forceps assisted delivery, neonatal asphyxia, and umbilical cord around the neck(all P<0.05). The pH value, arterial blood sample partial pressure(PaO2)and base excess(BE)values of the RH group were obviously lower than those of the control group(all P<0.01), while the arterial carbon dioxide partial pressure(PaCO2)was obviously higher than that of the control group(P<0.01). There were obvious differences in umbilical artery blood gas analysis indicators among children with different degrees of RH(P<0.05), and with the increase of the degree of RH, pH value, PaO2 and BE gradually decreased(P<0.05), and PaCO2 gradually increased(P<0.05). There was a negative correlation between the degree of RH and the pH of umbilical artery blood gas analysis(rs=-0.593, P<0.05). The results of multivariate Logistic regression analysis showed that delivery method, gestational hypertension, forceps assisted delivery, neonatal asphyxia, umbilical cord entanglement, pH, PaO2, PaCO2, and BE were all influencing factors for the occurrence of neonatal RH.CONCLUSION: There is a close correlation between neonatal RH and changes in umbilical artery blood gas analysis, and umbilical artery blood gas analysis can be used for the diagnosis of neonatal RH, which can be used to guide clinical treatment.
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The incidence of myopia among Chinese adolescents is progressively rising, indicating a distinct trend toward younger age onset.This paper aims to comprehensively review the impact of various visual performance on myopia and its progression, with a specific emphasis on accommodative function, convergence function, and ocular position. A meticulous exploration of accommodation function, encompassing accommodative amplitude, accommodative facility, accommodative response, positive relative accommodation, and negative relative accommodation, has been undertaken to elucidate its contributory role in myopia progression. Concurrently, an exhaustive analysis of convergence function has been conducted including esotropia and exotropia, convergence insufficiency and convergence excess, fusional function vergence, divergence insufficiency, and excess, providing a nuanced understanding of convergence's implications for myopia advancement. Furthermore, the influence of ocular position on myopia progression, along with other factors affecting perceptual ocular position and intermittent exotropia, is discussed. The primary objective of this article is to unveil the multifaceted visual performance influencing myopia and its progression, elucidating the paramount significance of accommodative function, convergence function, and ocular position in this context.
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Objective To investigate the characteristics and influencing factors of mental health status of permanent residents in Yichang, Hubei Province. Methods A total of 9 576 permanent residents aged 18 years and older from Yichang City were selected by a multistage random sampling method between June and October 2022. The PHQ-9 was used to assess the residents’ depressive symptoms, the GAD-7 was used to assess their anxiety symptoms, the ISI was used to assess their insomnia status, and the PCL-5 was used to assess their stress status. The influence factors of depression and anxiety were analyzed using χ2 test and logistic regression. Results A total of 9 122 valid questionnaires were completed. The detection rate of depression, anxiety, insomnia, and stress symptoms were 29.98%, 19.03%, 11.97% and 1.58%, respectively. Gender, education level, monthly family income, self-rated health status, mental health literacy level, total GAD-7 score, total ISI score, and total PCL-5 score were the main factors that caused residents' anxiety symptoms, while gender, education level, self-rated health status, total PHQ-9 score, total ISI score, and total PCL-5 score were the main factors that caused residents' anxiety symptoms. Conclusion The prevalence of depression and anxiety is high among the permanent residents in Yichang, while the situation of insomnia and stress is relatively good. Measures such as improving the level of mental health literacy can be taken to improve mental health level of residents in Yichang.
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Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.
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Objective Nowadays, radioactive xenon isotopes, including 131mXe, 133mXe, 133Xe, and 135Xe, are primarily released into the atmosphere through various reactor operation and major accidents of reactors. To improve the online monitoring capability of xenon in nuclear facilities and their gaseous effluents, a highly sensitive online xenon monitoring system was developed to monitor, warn, and alarm the activity concentration of radioactive xenon. Methods The online monitoring system for radioactive xenon gas in nuclear facilities was established using xenon membrane separation and concentration, xenon high-efficiency selective adsorption, and low-background gamma-ray spectrometry analysis methods. Results Under the operation mode of one-hour sampling and one-hour measuring, the minimum detectable activity concentration of the radioactive xenon online monitoring system for 133Xe was approximately (1.43 ± 0.03) Bq/m3. Conclusion This system can be effectively used for online monitoring of xenon activity concentration in nuclear facilities such as nuclear power plants and isotope production reactors, as well as in gaseous effluents. It helps improve the safety level of personnel, the environment, and nuclear facilities.
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Objective@#To analyze the relationship between the risk of tuberculosis outbreaks in schools and the visit interval of index cases, so as to provide a scientific reference for predicting the risks of tuberculosis outbreak and making preventive measures.@*Methods@#A total of 630 index cases from school tuberculosis outbreaks were studied during January, 2015 to December, 2022. Data on demographics, consultation history, etiological diagnosis, and methods of detection were collected. Restricted Cubic Splines (RCS), unconditional Logistic regression, and the receiver operating characteristic curve (ROC curve) were used for analysis.@*Results@#The RCS fitted curve showed that the risk of a tuberculosis outbreak linearly increased when the consultation interval for etiologically negative patients exceeded 5.79 days, or for etiologically positive patients exceeded 8.37 days. After multi factor adjustment, for every additional day in the visit interval of the index case, the odds ratio ( OR ) value for a high risk outbreak was 1.10 (95% CI =1.07-1.13)( P <0.05). When analyzed by tertiles of visit intervals, compared to an interval of <14 days, the OR values (95% CI ) for high risk outbreaks in schools with intervals of 14-<28 days and ≥28 days were 10.32(3.04-35.10) and 82.58( 28.42 -239.95), respectively( P <0.01), indicating a trend of increasing outbreak risk with longer visit intervals. Based on the ROC curve analysis, the optimal threshold for predicting a high risk school tuberculosis outbreak was 23.5 days, with an area under the curve ( AUC ) of 0.93 (95% CI =0.89-0.98).@*Conclusion@#An extended visit interval of index cases is a good early warning indicator for high risk tuberculosis outbreaks in schools and could be considered a key factor in early intervention and risk control strategies.
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AIM: To observe and analyze the effectiveness and safety of wearing corneal refractive therapy(CRT)and vision shaping treatment(VST)designed orthokeratology in controlling myopic progression in adolescents with low E-value corneal morphology.METHODS: This prospective study involved 100 cases(100 eyes)of adolescent myopia patients fitted with orthokeratology at our optometry clinic from January 2020 to December 2021. The data of right eye were collected for research, and they were divided into low myopia group(-1.00 to -3.00 D)and moderate myopia group(-3.25 to -5.00 D)according to spherical equivalent, with 50 cases in each group. Each group of patients was further randomly divided into the CRT group and the VST group, with 25 cases in each group. Uncorrected visual acuity, refractive error, axial length(AL), tear film break-up time(BUT), corneal endothelial cell density, corneal staining grading, lens decentration, and refractive power at 15°-30° were measured before and after wearing orthokeratology, with a follow-up duration of 1.5 a.RESULTS: The uncorrected visual acuity of CRT and VST subgroups in the low myopia group showed no statistical significance at any time point after wearing orthokeratology. However, in the moderate myopia group, CRT subgroup showed better uncorrected visual acuity than the VST subgroup, with significant differences at 1 d and 1 wk(t=-9.474, -12.067, both P<0.01); no significant differences were noted at other time points. After wearing lens for 6 mo and 1.5 a, the AL growth for the CRT subgroup in low and moderate myopia was less than the VST subgroup, with no statistically significant differences. There were no statistically significant differences in binocular BUT and corneal endothelial cell density after wearing lens for 6 mo and 1.5 a. Corneal injury was lower in the CRT subgroup than that in the VST subgroup, but the difference was not statistically significant(Z=-1.803, P=0.071). Lens decentration was significantly better in the CRT subgroup than in the VST subgroup(Z=-4.629, P<0.001). In the periphery of the retina at 15°-30°, there were no significant differences in the amount of myopic defocus between the two groups, while it was statistically significant at 1, 3, and 6 mo in the moderate myopia subgroup(t=-3.949, P=0.008; t=-5.833, P<0.001; t=-6.231, P<0.001), indicating that CRT subgroup could produce a greater amount of myopic defocus.CONCLUSION: For patients with low E-value corneal morphology, CRT, using the vector height at 8 mm on the cornea for fitting, is not limited to the corneal E-value. It shapes faster and improves uncorrected visual acuity after shaping, especially for moderate myopia, achieving better daytime vision. In terms of controlling myopia, CRT fitting elevates return zone depth(RZD), creating a small central optical zone to produce more peripheral myopic defocus. However, there was no significant difference between the two groups in controlling AL growth. Both groups showed minimal corneal damage, indicating consistent safety in myopia control.
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To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
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OBJECTIVE To design pharmaceutical care pathway for the problems related to chemotherapy， and to evaluate whether it contributes to the detection and intervention of drug-related problems （DRPs） in chemotherapy patients. METHODS The pharmaceutical care pathway table and flow charts were constructed and implemented by pharmaceutical care practice experience. The patients who were admitted to our hospital for chemotherapy before and after the implementation of the pharmaceutical care pathway were divided into control group （before the implementation，60 cases） and observation group （after the implementation，64 cases）， respectively； the relevant medical records of patients in the control group were extracted to evaluate DRPs， and pharmaceutical care of chemotherapy-related problems was performed for patients in observation group to extract DRPs. The basic condition， chemotherapy condition， DRPs classification and intervention status， adverse reactions induced by chemotherapy， PCNE classification of DRPs， occurrence time of DRPs， and drug classes related to DRPs were compared between 2 groups. RESULTS There was no statistical significance in the basic situation， chemotherapy regimen and chemotherapy drug category between the two groups （P＞0.05）. DRPs occurred in 46 and 37 patients in control group and observation group， respectively. In both groups， DRPs mainly occurred during chemotherapy， and mainly in the early stage of chemotherapy. Using the new pathway， the detection of DRPs significantly increased from 52.17% in the control group to 91.89% in the observation group （P＜0.05）. The successful intervention rate of DRPs was significantly increased from 32.61% in the control group to 72.97% in the observation group （P＜ 0.05）. The incidence of adverse drug reactions significantly decreased from 28.33% in the control group to 12.50% in the observation group（P＜0.05）. The main problem type of DRPs in the control group was treatment effectiveness， which mainly involved adjuvant antitumor drugs， mainly due to the use of adjuvant anti-tumor drugs for off-label prescribing； that of the observation group was treatment effectiveness and treatment safety， which mainly involved vomiting drugs， mainly due to insufficient medication to prevent nausea and vomiting caused by chemotherapy. CONCLUSIONS The implementation of the pathway helps clinical pharmacists to detect and intervene in DRPs among chemotherapy patients， and reduces the occurrence of chemotherapy-induced adverse reactions.
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ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.
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ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg-1）， Jieyu prescription （12.03 g·kg-1）， WJP （16.71 g·kg-1）， and fluoxetine （2.6 mg·kg-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.
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ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.
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Purpose@#Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. @*Materials and Methods@#Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints. @*Results@#Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy. @*Conclusion@#High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.
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Nine compounds were isolated from the crude extract of the solid culture of endophyte Trichoderma atroviride B7 of Colquhounia coccinea var. mollis by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and HPLC. They were identified as atroviridanol (1), 3-oxo-3-[(2-phenylethyl) amino]-propanoic acid (2), N-(2′-phenylethyl)-acetamide (3), neoechinulin A (4), echinulin (5), gancidin W (6), N-isobutyl-3-methylbutanamide (7), 5-acetamido-1-pentanol (8), and N-2-methylpropyl-2-methylbutenamide (9) by NMR, HR-MS, and so on. Among them, compound 1 is a new compound, and compounds 2-9 are firstly isolated from Trichoderma spp.
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AIM: To investigate the role and mechanism of N6-methyladenosine(m6A)methyltransferase 3(METTL3)in the pathogenesis of diabetic cataract.METHODS: We cultured SRA01/04 cells in low and high sugar media for 24h and measured changes in epithelial-mesenchymal transition(EMT)indicators(E-Cadherin, N-Cadherin, ZO-1 and α-SMA)using RT-qPCR and Western blot assays. Cell migration was also assessed using transwell and scratch assays. To investigate the expression level and localization of METTL3 in human lens anterior capsules tissues. Additionally, we used m6A dot blot assay to detect the m6A methylation level of cells cultured in low and high glucose media for 24h, and employed RT-qPCR and Western blot experiments to detect RNA and protein expression of METTL3 in cells. We then treated the cells with METTL3 inhibitor and measured changes in EMT markers by RT-qPCR and Western blot; m6A methylation level was detected by m6A dot blot test; cell migration was detected by Transwell. Finally, the expression of transforming growth factor-β(TGFβ1)in cultured cells was assessed by immunofluorescence staining and the expression levels of TGFβ1 and SNAIL in cells were determined using RT-qPCR and Western blot.RESULTS: Under high glucose conditions, the expression of EMT markers, METTL3, and m6A methylation levels were significantly increased in cells(P<0.05). Furthermore, the migratory ability of cells was higher in high-sugar medium than in low-sugar medium. In human lens anterior capsules, METTL3 expression was higher in patients with diabetic cataract compared to those with age-related cataract. Importantly, treatment with the METTL3 inhibitor STM2457 inhibited EMT in cells, the expression of TGFβ1 and SNAIL, as well as m6A methylation levels in cells(all P<0.05)compared to high-sugar + dimethyl sulfoxide(DMSO)group. Moreover, the migratory capacity of cells was reduced after the addition of STM2457 compared to the high-sugar + DMSO group.CONCLUSION:METTL3 promotes the EMT in human lens epithelial cells under high glucose conditions by activating the TGFβ1/SNAIL pathway, thus contributing to the development of diabetic cataracts.
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ObjectiveTo explore the effect of external diaphragm pacing therapy combined with abdominal functional electrical stimulation on respiratory function for stroke patients. MethodsFrom October, 2020 to September, 2022, 54 stroke patients were randomly divided into control group (n = 18), external diaphragm pacing group (n = 18) and combined treatment group (n = 18). All the groups received breathing training, while the external diaphragm pacing group received external diaphragm pacing therapy, and the combined treatment group received external diaphragm pacing and abdominal functional electrical stimulation therapy, for two weeks. They were measured forced vital capacity (FVC), forced expiratory volume in first second (FEV1), ratio of forced expiratory volume in first second in forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) with pulmonary function instrument; measured diaphragmatic excursion (DE) and diaphragmatic thickness (DT) with ultrasound, before and after treatment. ResultsThree cases in the control group, two cases in the external diaphragm pacing group and one case in the combined treatment group dropped off. The FVC, FEV1, PEF, MIP, MEP and DE improved in all the groups (|t| > 3.366, P < 0.01) after treatment; and the FVC, FEV1, MIP and DE increased more in the combined treatment group and the external diaphragm pacing group than in the control group (P < 0.05); the FVC and FEV1 increased more in the combined treatment group than in the external diaphragm pacing group (P < 0.05). ConclusionExternal diaphragm pacing therapy may improve ventilation and inspiratory muscle strength, and increase diaphragm movement for stroke patients; while the ventilation improved more after combining with abdominal functional electrical stimulation.
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As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.
Sujets)
Animaux , Médecine traditionnelle chinoise , Médicaments issus de plantes chinoises/usage thérapeutique , Modèles animaux , Angiopathies intracrâniennesRésumé
BACKGROUND@#Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.@*METHODS@#In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.@*RESULTS@#The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.@*CONCLUSIONS@#These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.
Résumé
OBJECTIVE@#To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme.@*METHODS@#The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests.@*RESULTS@#Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001).@*CONCLUSION@#For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.