Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

AIM: To analyse the prevalence and risk factors of dry eye among children aged 7-14 years in myopia prevention and control clinic.METHODS:A total of 222 children aged 7-14 years in myopia prevention and control clinic from December 2021 to February 2022 were included. General data of included children were collected, assessing the prevalence of dry eye by the ocular surface disease index(OSDI)scale and Keratograph 5M, and analyzing risk factors for dry eye occurrence by Logistic regression model.RESULTS:The prevalence of dry eye in children in myopia prevention and control clinic was 27.9%. Logistic Regression analysis showed that, allergic conjunctivitis(OR=2.31, 95%CI=1.12-4.78, P=0.02), refractive error(OR=5.57, 95%CI=2.40-12.94, P<0.01), use time of electronic >2h per day(OR=2.74, 95%CI=1.11-6.78, P=0.03), time of playing games >2h per day(OR=2.33, 95%CI=1.12-4.84, P=0.02), outdoor activity time ≤2h per day(OR=4.28, 95%CI=2.02-9.07, P<0.01)and sleep duration <8h per day(OR=3.23, 95%CI=1.44-7.27, P=0.01)were risk factors for dry eye among the children.CONCLUSIONS:The prevalence of dry eye among children in myopia prevention and control clinic should be paid high attention. Therefore, improving behavior habits and controlling the use time of visual display terminal products to prevent and slow down the occurrence of dry eye in children.

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Animals ; Mice ; Network Pharmacology ; AMP-Activated Protein Kinases ; Chromatography, High Pressure Liquid ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sirtuin 1 ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
Animals ; Mice ; Liver ; Aspartate Aminotransferases ; Bupleurum

Objective To investigate the spontaneous neural activity in the brain of patients with Alzheimer' s disease (AD) used 3 indicators of resting state-functional magnetic resonance (rs-fMRI) amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF) and percentage amplitude fluctuation (PerAF). Methods Totally 36 clinically diagnosed AD patients and 40 healthy volunteers were scanned by fMRI in resting state respectively. ALFF, fALFF and PerAF were used to calculate and compare the changes of brain regions between the two groups. Results Compared with the normal control group, mALFF value in AD group increased significantly in bilateral caudate nucleus, medial frontal gyrus, superior frontal gyrus, gyrus rectus, anterior cingulate gyrus, olfactive cortex, left middle frontal gyrus and inferior frontal gyrus (P<0. 05). mALFF values decreased significantly in the right middle temporal gyrus, inferior temporal gyrus, inferior occipital gyrus, middle occipital gyrus, bilateral calcarine, cuneus, lingual gyrus, superior occipital gyrus, vermis, precuneus and other regions (P<0. 05). In AD group, mfALFF value of right inferior temporal gyrus, anterior cerebellar lobe, fusiform gyrus, left superior frontal gyrus, medial frontal gyrus, middle frontal gyrus, inferior frontal gyrus, gyrus rectus and anterior cingulate gyrus increased significantly (P<0. 05); mfALFF values decreased significantly in bilateral lingual gyrus, left calcarine, cuneus, superior occipital gyrus, middle occipital gyrus and vermis (P<0. 05). In AD group, mPerAF value increased significantly in bilateral gyrus rectus, anterior cingulate gyrus, medial frontal gyrus, left superior frontal gyrus, caudate nucleus, middle frontal gyrus, inferior frontal gyrus, olfactive cortex and insula (P<0. 05); mPerAF values decreased significantly in bilateral calcarine, cuneus, superior occipital gyrus, lingual gyrus, precuneus, left fusiform gyrus, inferior occipital gyrus, right superior parietal lobule, angular gyrus, middle temporal gyrus, inferior temporal gyrus and middle occipital gyrus (P < 0. 05). Conclusion The default mode network (DMN) and visual network of AD patients are characterized by abnormal brain activity, with the most significant neural activity in the prefrontal cortex and visual cortex.

In the new situation,it puts forward the requirements for the construction of public hospitals'style,such as constructing the organizational system,leading the party building,maintaining the anti-corruption high pressure,improving the working system,strengthening the education of style,and cultivating the all-round supervision system.However,at this stage,there are still problems in the construction of public hospitals,such as imperfect institutions,insufficient play of the leading role of party building,inadequate understanding of medical personnel,low participation,lack of education in the style of work,low standardization,and insufficient use of information technology.By constructing and improving the organizational system and work-ing mechanism,tying the system cage,carrying out special work,strengthening the education of the profession,advanced demon-stration and guidance,strengthening social supervision,strict assessment,and fully operating information means,we can continu-ously improve the awareness of clean practice of medical personnel,improve the level of medical services,and improve the satis-faction of the people with medical treatment.

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.