ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

To evaluate the therapeutic effect of baicalein topical preparation on atopic dermatitis, we first constructed two atopic dermatitis-like mouse models induced by calcipotriol and 1-fluoro-2,4-dinitrobenzene to assess their therapeutic effect with skin tissue staining and other experiments. It was found that topical preparation of baicalein could alleviate epidermal thickening of diseased skin tissues, repair damaged skin barrier proteins, and inhibit T helper 2 cells (Th2) infiltration and mast cell infiltration and activation in lesional sites. Cyberpharmacology was utilized to analyze whether baicalein could treat atopic dermatitis by interfering with multiple pathogenesis-associated pathways. Results indicated that baicalein reduced the mRNA levels of inflammatory factors and inhibited the phosphorylation of NF-κB p65 and STAT1 proteins in keratinocyte cells. Together, the topical preparation of baicalein may be effective in alleviating atopic dermatitis-like symptoms in mice by down-regulating the phosphorylation level of NF-κB in keratinocytes, thereby decreasing the expression of inflammatory factors in keratinocytes, which provides an idea and a theoretical basis for the topical preparation of baicalein for the treatment of inflammatory skin diseases such as atopic dermatitis.

Nanozymes are a distinct category of nanomaterials that exhibit catalytic properties resembling those of enzymes such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Nanozymes derived from Chinese herbal medicines exhibit the catalytic functions of their enzyme mimics, while retaining the specific medicinal properties of the herb (termed "herbzymes"). These nanozymes can be categorized into three main groups based on their method of synthesis: herb carbon dot nanozymes, polyphenol-metal nanozymes, and herb extract nanozymes. The reported catalytic activities of herbzymes include POD, SOD, CAT, and GPx. This review presents an overview of the catalytic activities and potential applications of nanozymes, introduces the novel concept of herbzymes, provides a comprehensive review of their classification and synthesis, and discusses recent advances in their biomedical applications. Furthermore, we also discuss the significance of research into herbzymes, including the primary challenges faced and future development directions.
Nanostructures/chemistry* ; Humans ; Herbal Medicine/methods* ; Superoxide Dismutase/chemistry* ; Catalase/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Catalysis ; Glutathione Peroxidase/chemistry*

BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Objective To evaluate the effect of modulating gut microbiota for improving brain injury in rats with post-stroke depression.Methods Adult SD rats were randomized into normal control,middle cerebral artery occlusion(MCAO),post-stroke depression(PSD),PSD with fecal transplantation,PSD with antibiotics(rifaximin),PSD with probiotics(lactobacilli),and PSD with fluoxetine treatment groups(n=9).Neurological function scores of the rats were determined,and the changes in sugar water preference and immobility time in forced swimming test were observed;plasma levels of trimethylamine N-oxide(TMAO)and hydrogen sulfide(H2S)were detected with ELISA,Occludin,and the expressions of occludin,caudin-5 and IgG proteins I the brain tissues were determined using Western blotting.Results Compared with those in the control group,the rats in MCAO and PSD groups had significantly increased neurological function scores,TMAO level,the ratio of TMAO/H2S,and immobility time in forced swimming test with a lowered level of H2S(P<0.05).These changes were more obvious in PSD rats,which also exhibited a reduced sugar water preference with increased IgG protein and decreased occluding and caudin-5 expressions in the brain tissue(P<0.05).TMAO/H2S ratio in PSD rats was positively correlated with neurological function score(R2=0.3235,P=0.0269)and immobility time in swimming(R2=0.6290,P=0.0004)and negatively with sugar water preference(R2=-0.4534,P=0.0059).Treatment with fecal transplantation,antibiotics,probiotics and fluoxetine all significantly reduced neurological function scores,immobility time in forced swimming,TMAO/H2S ratio,and IgG protein expression and increased sugar water preference and brain occludin and caudin-5 expressions of the PSD rats(P<0.05).Conclusion In PSD rats,TMAO/H2S ratio is correlated with neurological function score,immobility time in forced swimming and sugar water preference,and modulating intestinal flora can improve neurological function and depressive symptoms and improve the integrity of the blood-brain barrier.

Objective To evaluate the effect of modulating gut microbiota for improving brain injury in rats with post-stroke depression.Methods Adult SD rats were randomized into normal control,middle cerebral artery occlusion(MCAO),post-stroke depression(PSD),PSD with fecal transplantation,PSD with antibiotics(rifaximin),PSD with probiotics(lactobacilli),and PSD with fluoxetine treatment groups(n=9).Neurological function scores of the rats were determined,and the changes in sugar water preference and immobility time in forced swimming test were observed;plasma levels of trimethylamine N-oxide(TMAO)and hydrogen sulfide(H2S)were detected with ELISA,Occludin,and the expressions of occludin,caudin-5 and IgG proteins I the brain tissues were determined using Western blotting.Results Compared with those in the control group,the rats in MCAO and PSD groups had significantly increased neurological function scores,TMAO level,the ratio of TMAO/H2S,and immobility time in forced swimming test with a lowered level of H2S(P<0.05).These changes were more obvious in PSD rats,which also exhibited a reduced sugar water preference with increased IgG protein and decreased occluding and caudin-5 expressions in the brain tissue(P<0.05).TMAO/H2S ratio in PSD rats was positively correlated with neurological function score(R2=0.3235,P=0.0269)and immobility time in swimming(R2=0.6290,P=0.0004)and negatively with sugar water preference(R2=-0.4534,P=0.0059).Treatment with fecal transplantation,antibiotics,probiotics and fluoxetine all significantly reduced neurological function scores,immobility time in forced swimming,TMAO/H2S ratio,and IgG protein expression and increased sugar water preference and brain occludin and caudin-5 expressions of the PSD rats(P<0.05).Conclusion In PSD rats,TMAO/H2S ratio is correlated with neurological function score,immobility time in forced swimming and sugar water preference,and modulating intestinal flora can improve neurological function and depressive symptoms and improve the integrity of the blood-brain barrier.

Objective To investigate the impact of acacetin(Aca)on angiogenesis in diabetes retinopathy(DR)rats by regulating Hippo signaling pathway.Methods Sixty SD rats were grouped into the control group,the DR group,the Aca low dose group(10 mg/kg),the Aca medium dose group(20 mg/kg),the Aca high dose group(30 mg/kg)and Hippo-YAP signaling pathway inhibitor Verteporfin group(Aca high dose 30 mg/kg+Verteporfin 0.8 pmol/kg),with 10 rats in each group.Except the control group,streptozotocin and high-fat feed were used to construct the DR model.Body weight and fasting blood glucose(FBG)levels of rats were measured.Fluorescein angiography(FFA)was applied to observe retinal angiogenesis and fluorescein leakage.Enzyme linked immunosorbent assay was applied to detect serum levels of vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2).Pathological changes of retinal tissue were observed by hematoxylin-eosin staining.Western blot assay was applied to detect expression levels of VEGF,hypoxia-inducible factor 1 alpha(HIF-1α),vascular cell adhesion molecule-1(VCAM-1)and Hippo signaling pathway proteins.Results Compared with the control group,retinal cells of rats in the DR group were arranged in a disordered and loose manner,with neovascularization and a large amount of fluorescein leakage,and body weight,the expression of large tumor suppressor homolog 2(LATS2),p-Yes-associated protein(YAP)were reduced.FBG and expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,transcription activator with PDZ binding motif(TAZ),TEA domain family member 1(TEAD1)were increased(P＜0.05).Compared with the DR group,retina cells of rats in the Aca low,medium and high-dose groups and the Verteporfin group were arranged neatly,with reduced neovascularization and fluorescence leakage,body weight and the expression levels of LATS2 and p-YAP were increased,and FBG,expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,TAZ and TEAD1 were reduced(P＜0.05).The effect was more obvious in the Aca high dose group.However,there was no significant difference in each indicator between the Verteporfin group and the Aca high dose group.Conclusion Aca can inhibit angiogenesis and improve retinal pathological damage in DR rats,and its mechanism of action may be related to regulating the Hippo signaling pathway.

Objective:To investigate the effects of 2 650 MHz radiofrequency (RF) exposure on the behavior and neurotransmitter release of mice.Methods:Adult male C57BL/6N mice were divided into a normal control (CON) group and a radiofrequency radiation (RFR) group using the random number table method. The mice in the RFR group were subjected to single-dose whole-body exposure to a uniform 2 650 MHz RF electromagnetic field for 3 h. During the RF exposure, the field strength in the effective working area of the RF radiation platform was measured using an electromagnetic radiation analyzer, and the changes in the anal temperature of the mice were monitored using an optical fiber thermometer. Moreover, the changes in the cognition, social interaction, and emotion of the mice were determined through the new object recognition test, social preference test, and open field test. Finally, the changes in the hippocampal neurotransmitter release levels of the mice were detected using microdialysis sampling and mass spectrometry, and the changes in the hippocampal tissue structure and ultrastructure were observed via microscopy.Results:Under the test conditions, RF radiation improved the anal temperature of the mice, with a maximum increasing amplitude of 0.61℃, falling within the range of thermal safety. The mice in the RFR group experienced a significant decrease in the frequency and time for exploring new objects ( t=4.50, 2.53, P < 0.05) in the new object recognition test, a significant decrease in the frequency ( t=0.08, P<0.01) and time ( t=0.03, P<0.05) for exploring other mice in the social preference test, and no significant change in the frequency and time for exploring the central area ( P > 0.05) in the open field test. Compared to the CON group, the RFR group showed an increase in the release of 5-hydroxytryptamine (5-HT) ( t=-2.56, P < 0.05) and a decrease in the release of acetylcholine (ACh) ( t=2.21, P < 0.05), no significant difference in the release of glutamate (Glu) and γ-aminobutyric acid (GABA) ( P > 0.05), and no evident damage to the hippocampal tissue and structure and synaptic ultrastructure. Conclusions:2 650 MHz RF radiation may induce cognitive impairment and abnormal social preference in mice, which is attributed to neuronal dysfunctions and neurotransmitter release disorders under RF exposure.

Objective To explore the flow chart and key points of etiological differential diagnosis of character"卜"sign in fetal three-vessel and trachea(3VT)view.Methods A retrospective study was performed on ultrasound images of 37 fetuses,who had"卜"sign in 3VT view during fetal heart ultrasound scanning in The Affiliated Suzhou Hospital of Nanjing Medical University from Aug.2020 to Oct.2023.The types of diseases with"卜"sign and the flow chart and key points of differential diagnosis were summarized.All cases were diagnosed by 2 experienced senior prenatal ultrasound doctors independently.Results The incidence of"卜"sign was 0.14％(37/27 019).Among the 37 fetuses with"卜"sign on 3VT view,13(35.14％)cases had complete transposition of great arteries(TGA),11(29.73％)had double outlet of right ventricle with abnormal relationship of great arteries(DORV/AA),7(18.92％)had truncus arteriosus(TA,van Praagh A1,A2 and A3),and 6(16.22％)had pulmonary atresia with ventricular septal defect(PA/VSD).During the process of differential diagnosis,the presence or absence of aorta and pulmonary arteries,the ventricle-artery connection relationship,and the blood supply to both lungs should be focused on,and the final diagnosis can be derived step by step according to the flow chart.The key points of differential diagnosis were as follows:the ventricle-artery connection was inconsistent in TGA;in DORV/AA both aorta and pulmonary artery were entirely or mostly from right ventricle without normal spiral relationship;in TA only a common artery trunk was detected,and main pulmonary artery or its branches were from the artery trunk;and in PANSD pulmonary artery was atresia and only aorta was detected,and the blood supply to both lungs was from ductus arteriosus and/or aortopulmonary collateral arteries.Conclusion The fetal differential diseases with"卜"sign in 3VT view include TGA,DORV/AA,TA(van Praagh A1,A2 and A3),and PA/VSD.Understanding the flow chart and key points of differential diagnosis can improve the prenatal detection rate and diagnosis of related malformations.