Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE^-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology* ; Growth Differentiation Factor 15/metabolism* ; Animals ; Biphenyl Compounds/pharmacology* ; Endoplasmic Reticulum Stress/drug effects* ; Activating Transcription Factor 4/genetics* ; Mice ; Humans ; Male ; Magnolia/chemistry* ; CCAAT-Enhancer-Binding Proteins/genetics* ; Mice, Inbred C57BL

Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.

ObjectiveTo explore the impact of COVID-19 epidemic on the lifestyles of patients with chronic diseases and to help better chronic disease prevention and control during the epidemic. MethodsThe patients with hypertension and type 2 diabetes who were still under management in Baoshan District， Shanghai at the end of September 2019 were selected for the investigation through telephone follow-up from March 1 to April 30 in 2020. 960 participants were selected using a stratified random sampling method. Those who did not complete the investigation for any reasons were excluded. A total of 613 people were effectively investigated. We compared and analyzed the lifestyles of patients with chronic diseases during 2020 （COVID-19） with those in 2019. ResultsDuring the epidemic， the proportion of people who had regular physical exercise （P<0.05）and transportation activities（P<0.05） was lower than that before the epidemic. The proportion of people with light， moderate and heavy activity intensity（P<0.05） was lower than before the epidemic， and the difference was statistically significant. The time spent on sitting or leaning was more than that before the epidemic （P<0.05）. As for the condition of complying with the doctor’s advice， no significant difference was found in different age and chronic disease groups. There was a statistically significant difference in total food intake （χ²=7.994，P<0.05） and staple foods （χ²=6.677，P<0.05） between patients with or without hypertension. There was a statistically significant difference in total food intake（χ²=10.694，P<0.05） and staple food intake （χ²=9.523，P<0.05） between those with or without diabetes mellitus（P<0.05）. Patients with chronic diseases during the epidemic could not know about latest values of measurement index and had emotional problems such as restlessness， nervousness and irritability. ConclusionPatients with chronic diseases changes their lifestyles during the epidemic， and their exercise and travel conditions decrease during the COVID-19 lockdown period. Most patients have different levels of emotional problems such as restlessness and nervousness. It is recommended to increase the intensity and frequency of physical activity and promote mental health to better prevent and control the occurrence of chronic diseases.

Objective:To analyze the satisfaction of referral patients for the medical services provided by the countywide medical community, for reference in further improving its quality and continuity of medical services.Methods:From April to July 2021, a systematic sampling method was adopted to selected the survey subjects from the outpatients from the leading hospitals and three affiliated units of two medical communities, as well as those from two county-level hospitals of non medical communities and five grass-roots medical and health institutions. A total of 660 patients were included in the questionnaire survey. The questionnaire covered key demographic information and 15 satisfaction questions under 4 dimensions. The propensity score matching method was used to reduce confounding factors, factor analysis was used to calculate the satisfaction of referral patients in the medical community group and the non-medical community group, and the systematic dynamics approach was used to analyze the effect of patient satisfaction on referral intention.Results:A total of 641 valid questionnaires were collected. Based on a 1∶2 propensity score matching, 591 patients were finally enrolled, consisting of 102 up-referral cases from the non-community group and 273 such cases from the community group, as well as 76 down-referral cases from the non-community group and 140 such cases from the community group. The overall satisfaction scores by both up and down referral patients were 4.26(1.01)and 4.29(1.14)respectively.The overall satisfaction, medical service satisfaction, technical service quality satisfaction and non-technical service quality satisfaction of up-referral patients, as well as the overall satisfaction, non-technical service quality satisfaction of down-referral patients of the community group were higher than those from the non-community group, with differences statistically significant( P<0.05). The higher satisfaction of patients with their referral in the community, the stronger their referral willingness. Conclusions:The overall satisfaction of refrerral patients in the medical community group is higher than that of the non medical community group. The construction of county medical community has promoted the improvement of satisfaction of referral patients. However, it is still imperative to encourage high-quality medical resources to support primary institutions, to enhance the service level of primary medical and health institutions, to implement differentiated medical insurance reimbursement policies, and to improve the continuity of medical services within the community.

Biosynthesis of nanomaterials has attracted much attention for its excellent characteristics such as low energy consumption, high safety, and environmental friendliness. As we all know, the toxic selenite can be transformed into higher-value nanomaterials by using bacteria. In this study, nano-selenium was synthesized by halophilic Bacillus subtilis subspecies stercoris strain XP in LB medium supplemented with selenite (electron acceptor). The physicochemical characteristics of nano-selenium were analyzed by scanning electron microscope (SEM), X-ray energy dispersive spectral analysis (EDAX), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). Meanwhile, the antifungal activity of nano-selenium to strawberry pathogens (fusarium wilt, erythema, and purple spot fungi) was determined. The products from reduction of selenite by strain XP was amorphous spherical selenium nanoparticles (SeNPs) with a diameter range of 135-165 nm. The production of SeNPs was positively correlated with time (0-48 h) and no changes were observed on cell morphology. Selenium was dominant in the surface of SeNPs where the organic elements (C, O, N, and S) existed at the same time. SeNPs were coated with biomolecules containing functional groups (such as -OH, C=O, N-H, and C-H) which were associated with the stability and bioactivity of particles. Although the highest concentration of SeNPs had significant (P<0.05) inhibitory effects on three strains of strawberry pathogens, antifungal activity to erythema and fusarium wilt pathogenic fungi was higher than that to purple spot pathogenic fungi from strawberry. In conclusion, strain XP not only has strong tolerance to high salt stress, but can be also used to synthesize biological SeNPs with good stability and biological activity. Thus, the strain XP has bright perspectives and great potential advantage in pathogens control and green selenium-rich strawberry planting as well as other fields.
Bacillus subtilis ; Fragaria ; Nanoparticles ; Selenious Acid ; Selenium

Objective:To investigate the effect of miR-424-5p on radiosensitivity and its mechanism in cervical cancer patients.Methods:The expression levels of miR-424-5p in the cervical cancer tissues and Hela cells were detected by RT-qPCR. The apoptosis rate of Hela cells was determined by flow cytometry. The proliferation activity of Hela cells was detected by CCK-8 assay. The protein expression levels in Hela cells were measured by Western blot.Results:Compared with normal tissues and cells, the expression level of miR-424-5p was significantly down-regulated in the cervical cancer tissues and Hela cells (1.03 vs. 0.88, P<0.01; 1.00 vs. 0.75, P<0.01). Overexpression of miR-424-5p significantly inhibited the proliferation activity of Hela cells after radiation treatment ( P<0.01), and significantly increased the apoptosis rate of Hela cells after radiation treatment (24.82% vs. 49.94%, P<0.001). Overexpression of miR-424-5p inhibited HMGA1 expression (1.01 vs. 0.63, P<0.01). miR-424-5p directly affected HMGA1, thereby impacting the radiosensitivity of cervical cancer radiotherapy. Conclusion:miR-424-5p can improve the radiosensitivity of cervical cancer radiotherapy by directly targeting HMGA1.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Objective:To evaluate the clinical effects of orthokeratology lens on children with myopic anisometropia.Methods:Retrospective case series study. The data of 226 myopic anisometropia children, (10.83±1.56)years old, including 95 males and 131 females, fitted with orthokeratology(OK) lens in Beijing Tongren Hospital from June 2017 to June 2019 were collected. According to the lens wearing condition and baseline anisometropia, they were divided into four groups: group A1 with an average age of (10.68±1.66) years (bilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 50 males and 61 females), group A2 with an average age of (11.24±1.38) years (bilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 10 males and 23 females), group B1 with an average age of (10.79±1.51) years (unilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 17 males and 21 females) and group B2 with an average age of (10.97±1.60) years (unilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 18 males and 26 females). After wearing OK lens for one year, the changes of axial length(AL) and AL difference were observed and statistically analyzed.Results:(1) AL changes: after wearing OK-lens for one year, AL of each eye increased. In group A1, the AL of the more myopic eyes and the less myopic eyes increased by (0.20±0.21) mm and (0.24±0.22) mm respectively, and the difference was statistically significant ( t=-3.208, P=0.002); in group A2, the AL growth of the more myopic eyes and the less myopic eyes were (0.04±0.11) mm and (0.17±0.14) mm, and the difference was statistically significant ( t=-5.545, P<0.001). In group B1, the AL elongation of the more myopic eyes and the less myopic eyes were (0.14±0.21) mm and (0.39±0.23) mm, and in group B2, the AL growth of the more myopic eyes and the less myopic eyes were (0.11±0.14) mm and (0.54±0.24) mm, with statistically significant differences( t=-6.533, -11.643; all P<0.001). There was a linear correlation between AL elongation and age of the more myopic eyes and the less myopic eyes in group A1(corrected R 2=0.208, 0.237) and group A2 (corrected R 2=0.169, 0.360). There was no linear correlation of the more myopic eyes and the less myopic eyes between AL change and age or baseline myopia in group B1 ( F=0.514, 1.205; P=0.602, 0.312) and group B2 ( F=0.841, 0.056; P=0.439, 0.946). (2)Change of AL difference: after wearing OK lens for one year, the changes of AL difference in groupA1, A2, B1 and B2 were (-0.04±0.14) mm,(-0.13±0.13) mm,(-0.26±0.24) mm and (-0.43±0.25) mm, and the decrease of AL difference in moderate and high anisometropia groups were greater than that in low anisometropia groups ( t =-3.211, -3.180; P=0.002, 0.002).There was a linear correlation between the reduction of AL difference and baseline anisometropia in group A1, A2 and B2 (corrected R 2=0.099, 0.149, 0.230), and there was no linear relationship between the decrease of AL difference and the baseline anisometropia in group B1 ( F=0.014, P=0.908). Conclusions:Orthokeratology could effectively control the progression of myopia and to treat anisometropia. The effect of myopia control was better in the older binocular OK lens wearers, and for the patients with greater baseline anisometropia, the treatment effect of anisometropia was better.

Objective:To evaluate the clinical effects of orthokeratology lens on children with myopic anisometropia.Methods:Retrospective case series study. The data of 226 myopic anisometropia children, (10.83±1.56)years old, including 95 males and 131 females, fitted with orthokeratology(OK) lens in Beijing Tongren Hospital from June 2017 to June 2019 were collected. According to the lens wearing condition and baseline anisometropia, they were divided into four groups: group A1 with an average age of (10.68±1.66) years (bilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 50 males and 61 females), group A2 with an average age of (11.24±1.38) years (bilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 10 males and 23 females), group B1 with an average age of (10.79±1.51) years (unilateral OK lens wearing with low anisometropia, 1.0 D≤SE difference<2.5 D, 17 males and 21 females) and group B2 with an average age of (10.97±1.60) years (unilateral OK lens wearing with moderate and high anisometropia, SE difference≥2.5 D, 18 males and 26 females). After wearing OK lens for one year, the changes of axial length(AL) and AL difference were observed and statistically analyzed.Results:(1) AL changes: after wearing OK-lens for one year, AL of each eye increased. In group A1, the AL of the more myopic eyes and the less myopic eyes increased by (0.20±0.21) mm and (0.24±0.22) mm respectively, and the difference was statistically significant ( t=-3.208, P=0.002); in group A2, the AL growth of the more myopic eyes and the less myopic eyes were (0.04±0.11) mm and (0.17±0.14) mm, and the difference was statistically significant ( t=-5.545, P<0.001). In group B1, the AL elongation of the more myopic eyes and the less myopic eyes were (0.14±0.21) mm and (0.39±0.23) mm, and in group B2, the AL growth of the more myopic eyes and the less myopic eyes were (0.11±0.14) mm and (0.54±0.24) mm, with statistically significant differences( t=-6.533, -11.643; all P<0.001). There was a linear correlation between AL elongation and age of the more myopic eyes and the less myopic eyes in group A1(corrected R 2=0.208, 0.237) and group A2 (corrected R 2=0.169, 0.360). There was no linear correlation of the more myopic eyes and the less myopic eyes between AL change and age or baseline myopia in group B1 ( F=0.514, 1.205; P=0.602, 0.312) and group B2 ( F=0.841, 0.056; P=0.439, 0.946). (2)Change of AL difference: after wearing OK lens for one year, the changes of AL difference in groupA1, A2, B1 and B2 were (-0.04±0.14) mm,(-0.13±0.13) mm,(-0.26±0.24) mm and (-0.43±0.25) mm, and the decrease of AL difference in moderate and high anisometropia groups were greater than that in low anisometropia groups ( t =-3.211, -3.180; P=0.002, 0.002).There was a linear correlation between the reduction of AL difference and baseline anisometropia in group A1, A2 and B2 (corrected R 2=0.099, 0.149, 0.230), and there was no linear relationship between the decrease of AL difference and the baseline anisometropia in group B1 ( F=0.014, P=0.908). Conclusions:Orthokeratology could effectively control the progression of myopia and to treat anisometropia. The effect of myopia control was better in the older binocular OK lens wearers, and for the patients with greater baseline anisometropia, the treatment effect of anisometropia was better.

ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.