AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Objective To investigate the changes of sex hormone levels in polycystic ovary syndrome(PCOS)in infertile population after the assisted reproductive technology treatment,and to provide an evidence for the choice of the treatment.Methods The medical data of patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2016 to June 2021 were collected and divided into PCOS group(103)and non-PCOS group(589)according to whether they were diagnosed with PCOS,and the sex hormone changes of the two groups were compared.Results The patients in PCOS group were younger and had the higher BMI,more sinus follicles,higher AMH value,and lower total Gn usage.The number of LH/FSH>2 in PCOS group was higher than that in non-PCOS group(P<0.05).After the treatment,LH in both groups decreased,FSH,E2 and(P<0.05)increased;The difference of LH and E2 before and after the treatment in PCOS group was greater than that in non-PCOS group<0.05).Conclusion Compared with non-PCOS infertile patients,the changes of sex hormone indexes in PCOS infertile patients before and after the treatment were more obvious.In order to obtain the better clinical effect in patients with polycystic ovaries,it is recommended to pay attention to the changes of related sex hormone levels in the course of subsequent treatment,and choose a reasonable treatment plan.

Objective To investigate the effect of electromagnetic wave power density on the expression of glial fibrillary acidic protein(GFAP)in the hippocampus of SD rats under 1800 MHz electromagnetic wave irradiation,and whether it exhibits a"window effect".Methods Ninety-eight 4-week-old SPF-grade SD rats were randomly divided into 14 groups,with 7 rats in each group.Seven groups were exposed groups(frequency:1800 MHz,power densities:0.1 mW/cm2,0.3 mW/cm2,0.5 mW/cm2,0.7 mW/cm2,0.9 mW/cm2,1.0 mW/cm2,1.2 mW/cm2)and corresponding 7 groups were control groups(power density:0 mW/cm2).Exposure was conducted for 12 hours daily for 3 weeks.After exposure,Western Blot was used to detect the expression level of GFAP in the hippocampal tissue,and immunohistochemistry staining was performed to determine the average optical density(MOD)value of GFAP-positive expression products in the DG,CA3,and CA1 regions of the hippocampal tissue,to determine the power density window of GFAP expression in the hippocampus of SD rats under 1800 MHz exposure.Results At power densities of 0.1 mW/cm2 and 0.3 mW/cm2,Western Blot results showed increased expression of GFAP in the rat hippocampus(P<0.05),and immunohistochemistry staining demonstrated increased MOD values of GFAP in the three regions(P<0.05).Conclusion Long-term exposure to 1800 MHz elect-romagnetic radiation has a"window effect"on the expression of GFAP in the DG,CA3,and CA1 regions of the hippocampus in SD rats,with power density windows of 0.1 mW/cm2 and 0.3 mW/cm2.

BACKGROUND:Despite a series of clinical treatment measures,the treatment of pulmonary fibrosis still faces challenges.In recent years,mesenchymal stem cells and their extracellular vesicles have attracted extensive attention as an emerging therapeutic strategy and are considered to be a promising means of treating pulmonary fibrosis. OBJECTIVE:To systematically review the application of mesenchymal stem cells and their extracellular vesicles in the treatment of pulmonary fibrosis,to comprehensively understand their therapeutic mechanism,efficacy evaluation and problems,and provide reference and guidance for further research and clinical application in the future. METHODS:Using Chinese and English search terms"mesenchymal stem cells","mesenchymal stem cell extracellular vesicles","pulmonary fibrosis",we searched the CNKI and PubMed electronic journal databases.By means of manual reading and eliminating duplicate articles,112 articles were selected,but 58 Chinese and English articles were finally included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells and their extracellular vesicles have shown great potential in the treatment of pulmonary fibrosis,such as regulating inflammatory responses,inhibiting fibroblast proliferation,and promoting damaged tissue repair.Preliminary results from clinical trials have also shown some effects of the treatment,including improved lung function and quality of life in patients.(2)However,mesenchymal stem cells and extracellular vesicles in the treatment of pulmonary fibrosis still face some challenges.During treatment,technical challenges such as cell migration and intrachistological localization need to be addressed for it to accurately reach the damaged lung tissue.Furthermore,its long-term safety also needs to be further studied and improved.For translational medicine development,standardized procedures such as cell collection,cell isolation,cell culture,cell harvesting,and cell identification need to be refined.(3)Despite these challenges,through the joint efforts of scientific researchers and medical personnel,these problems are expected to be gradually solved.In the future,we can further improve treatment outcomes by optimizing treatment regimens and exploring individualized treatments.At the same time,in-depth research on the therapeutic mechanism of stem cells and their extracellular vesicles is expected to develop more efficient and safe therapeutic strategies.

Objective:To investigate the intelligence status of children aged 10 - 12 in rural areas of Linxia Hui Autonomous Prefecture (referred to as Linxia) in Gansu Province.Methods:From September to November 2019, a cross-sectional study was carried out to investigate the intelligence status of children aged 10 to 12 in 8 counties (cities) of Linxia. Chinese Raven's Progressive Matrices (rural version) was used for intelligence test and children's intelligence quotient (IQ) was calculated by regular mold to evaluate children's intelligence level.Results:A total of 1 721 children in Linxia were tested for intelligence, with an average IQ of 103.2. Among them, low intelligence (≤69) accounted for 1.0% (18/1 721), borderline (70 - 79) accounted for 3.0% (52/1 721), middle and lower (80 - 89) accounted for 8.4% (144/1 721), moderate (90 - 109) accounted for 56.6% (974/1 721), middle and upper (110 - 119) accounted for 21.9% (377/1 721), excellent (120 - 129) accounted for 7.8% (135/1 721), extremely excellent (≥130) accounted for 1.2% (21/1 721). There were 635, 598 and 488 children aged 10, 11 and 12, respectively, with an average IQ of 106.1, 103.3 and 99.2. There were 919 males and 802 females, with an average IQ of 102.9 and 103.4, respectively.Conclusion:In 2019, the intelligence of children aged 10 to 12 in rural areas of Linxia has reached the moderate level.

Objective To investigate sex-related differences in left ventricular systolic dysfunction in heart failure with preserved ejection fraction(HFpEF)and type 2 diabetes mellitus(T2DM).Methods A total of 228 HFpEF patients who were treated in the Department of Endocrinology and Cardiology of the Second Hospital of Shijiazhuang from January 2019 to June 2023 were enrolled.They were divided into HFpEF group[women(n=61),men(n=73)]and HFpEF+T2DM group[women(n=49),men(n=73)]according to whether they had T2DM.Conventional echocardiography and left ventricular global longitudinal strain(GLS)data were measured.Sex-related differences of left ventricular structure and function were compared between the two groups.Multivariable linear regression analysis was performed for the determinants of impaired left ventricular GLS for HFpEF with T2DM patients and HFpEF patients of both sexes.Results LVMI was lower in women than in men in HFpEF group(P<0.05).The left ventricular remodeling rate of women was higher in HFpEF+T2DM group than that of men and women in HFpEF group,and the GLS of women was lower than that of men and women in HFpEF group(P<0.05).The E/E'was higher in women than in men in HFpEF and HFpEF+T2DM groups(P<0.05).Multivariable linear regression analysis showed that age,women,HbA1c and LVMI were the determinants of GLS impairement in HFpEF patients with T2DM.Age,T2DM,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF women patients,where as age,BMI,CHD,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF men patients.Conclusions There are sex-related differences in left ventricular systolic dyfunction in HFpEF with T2DM patients.With T2DM exerting a greater adverse effect onleft ventricular systolic dyfunction in women with HFpEF than men.

Objective To explore the differences in efficacy and safety of drug selection based on pharmacogenomics and evidence-based medicine for treatment-resistant schizophrenia(TRS).Methods A total of 100 patients with TRS in our hospital from January 2023 to October 2023 were divided into observation group(gene-oriented antipsychotic drug selection group,22 males and 28 females)and control group(evidence-based medicine oriented antipsychotic drug selection group,23 males and 27 females).Oral mucosal epithelial cells of the observation group were noninvasive collected with a sampling brush and antipsychotic drug gene detection was performed.Antipsychotic drugs with normal metabolism,good response and little toxic side effects were selected according to the test results,and the drugs of the control group were selected by the designated physician on the basis of the Chinese Guidelines for the Prevention and Treatment of Schizophrenia,2015 revision.Antipsychotic efficacy was evaluated before treatment and 4 weeks,8 weeks after treatment with positive and negative syndrome scale(PANSS).Treatment emergent symptom scale(TESS)was used to assess adverse reactions at the 4th and 8th weekend after treatment.Results After 8 weeks of treatment,the incidence of adverse reactions in central nervous system,autonomic nervous system,endocrine system,circulatory system and digestive system in the control group was higher than that in the observation group.The difference was remarkable.The scores of positive symptoms,negative symptoms and general psychopathological symptoms between the observation group and the control group at baseline were basically the same(P>0.05).After 4 weeks of treatment,the scores of positive symptoms,negative symptoms and general psychopathological symptoms in the observation group were lower than those in the control group.The difference was remarkable.After 8 weeks of treatment,the scores of positive symptoms,negative symptoms and general psychopathological symptoms in the observation group were lower than those in the control group.The difference was remarkable.At the end of the 8th week after treatment,the effective rate of the observation group was higher than that of the control group,the difference was remarkable(44%vs.24%,P=0.035).Two-factor repeated measurement analysis of variance was used,indicating that PANSS scores of the two groups changed with time at baseline,4 weeks and 8 weeks after treatment,and the difference was remarkable(F-time=697.139,P<0.05);The difference of PANSS among groups was remarkable(F-groups=5.398,P<0.05);PANSS score was different with different treatment methods,and the difference was remarkable(F-interaction=3.008,P<0.05).Conclusion Gene-directed antipsychotic selection maybe is superior to evidence-based antipsychotic selection in improving effective rate and reducing adverse drug reactions.

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and patho-logical conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of＞1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in N-desethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal infor-mation for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

Background: Patients with functional dyspepsia (FD) are accompanied by different degree of psychological stress, and clinicians usually have insufficient quantitative assessment of patients’psychological stress. Aims: To explore the effect of psychological stress assessed by 4-item perceived stress scale (PSS-4) and 10-item perceived stress scale (PSS-10) on dyspepsia symptoms, anxiety, depression, somatization and quality of life in FD patients. Methods: A total of 357 FD patients met Rome IV criteria from March 2021 to March 2022 at Affiliated Hospital of North Sichuan Medical College were recruited. Score of PSS-4, PSS-10, generalized anxiety disorder-7 (GAD-7), patient healthy questionnaire-9 (PHQ-9), adapted patient healthy questionnaire-15 (adapted PHQ-15), dyspepsia symptom severity (DSS), Nepean dyspepsia index-short form (NDI) were performed. Effects of PSS-4, PSS-10 on dyspepsia symptoms, anxiety, depression, somatization and quality of life in FD patients were analyzed. Results: Correlation analysis showed that PSS-4 (r=0.152, P=0.004) and PSS-10 (r=0.194, P=0.000) were correlated with DSS; PSS-4 (r=0.341, P=0.000) and PSS-10 (r=0.389, P=0.000) were correlated with adapted PHQ-15; PSS-4 (r=0.239, P=0.000) and PSS-10 (r=0.327, P=0.000) were correlated with NDI; PSS-4 (r= 0.561, P=0.000) and PSS-10 (r=0.680, P=0.000) were correlated with anxiety; PSS-4 (r=0.449, P=0.000) and PSS-10 (r= 0.524, P=0.000) were correlated with depression. Multiple linear regression analysis showed that psychological stress assessed by PSS-4 (β=0.180, P=0.000), DSS (β=0.390, P=0.000) and FD classification (β=-0.116, P=0.024) were the influencing factors of NDI, and the psychological stress assessed by PSS-10 (β=0.268, P=0.000), DSS (β=0.360, P=0.000) and FD classification (β=-0.116, P=0.021) were the influencing factors of NDI. Conclusions: Psychological stress assessed by PSS-4, PSS-10 have effects on anxiety, depression, somatization, DSS and NDI in FD patients, and PSS-4 is shorter. These results suggest that PSS-4 can be used clinically to assess quickly and initially the impact of psychological stress on FD patients.

Objective:To clarify the clinical characteristics and related fators of children with delayed antibody production of mycoplasma pneumoniae pneumonia(MPP).Methods:Two hundreds and eithty-five cases of children hospitalized at Children′s Hospital of Soochow University with MPP(positive for nucleic acid testing of respiratory secretion)were chosen from January 1st, 2019 to September 31st, 2019.Delayed antibody production group included 36 cases, who were tested for negative IgM antibody meanwhile the titer of IgG antibody changed less than 4 folds within 14 days.Positive group included 249 cases who were tested for positive IgM antibody or the titer of IgG antibody changed over 4 folds within 14 days.The characteristics of clinical manifestation, immunology and radiology were comparatively analyzed.Results:The medium age of delayed antibody production group was 0.75(0.30, 2.78)years old, which was obviously younger than that from positive group[5.50(3.73, 7.20)years old]( P<0.001). Low level of serum immunoglobulin IgG was the independent effect factor of delayed production for Mycoplasma pneumoniae antibody( P=0.037). When the serum immunoglobulin IgG level was lower than 7.155mmol/L, the sensitivity of predicting delayed production for mycoplasma pneumoniae antibody would be 0.819 and the specificity was 0.833.The underlying diseases associated with delayed antibody production were hospitalization history during neonatal period( P=0.007)and congenital heart disease( P=0.001). There were 11.11%(4/36)of children appearing spasmodic cough, 41.67%(15/36)of children showing wheezing and 33.33%(12/36)showing diarrhea in delayed antibody group, which were significantly higher than those in positive group[0.40%(1/249), 24.50%(61/249)and 9.64%(24/249), respectively, P<0.05]. The incidence of fever in delayed antibody group were 63.89%(23/36), which was lower than that in positive group[92.37%(230/249)]( P<0.001), meanwhile, the fever last time was 2.50(0, 4.75)days in delayed antibody group, which was shorter than that in positive group[ 7(5.00, 8.50)days]( P<0.001). In the delayed antibody group, there was 19.44%(7/36)of children sufferring from lobar pneumonia, and no extrapulmonary manifestations occurred, which were significantly lower than those in positive group[75.50%(188/249), 14.86%(37/249)]( P<0.05). Conclusion:Delayed antibody production in children with MPP is more common when serum immunoglobulin IgG level is lower than 7.155 mmol/L, especially in the presence of neonatal hospital history and congenital heart disease.The clinical manifestations of these children are mainly characterized by spasmodic cough and wheezing, with low probability of fever, lobular pneumonia and extrapulmonary manifestations.