Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

Objective Search and collect the previous relevant literature on the influence of diabetes on the progress of tendinosis,summarize the relevant conclusions and discuss the pathogenesis of diabetes accelerating the progress of tendinosis,mainly including summarizing the biomechanical and histological changes of diseased tendons in diabetes patients,as well as its pathogenesis at the cellular level.Methods This paper reviewed and analyzed the domestic and foreign literature related to dia-betes tendinosis by searching some Chinese and English databases like PubMed,Springer Link,CNKI,Google Academic.Re-sults Most previous studies more support the theory of degeneration as the pathogenesis of tendinosis,but now more and more researchers find that diabetes,as a systemic metabolic disease,can induce the occurrence of tendinosis through a variety of mech-anisms,or aggravate the progress of tendinosis,such as the accumulation of advanced glycation end products(AGEs)at the le-sion site,chronic inflammatory reaction at the lesion site,increased oxidative stress level of tendon cells And changes in the ac-tivities of matrix metalloproteinases and glutamine transaminase.By summarizing and analyzing the various understandings of dia-betes on the pathogenesis of tendinosis proposed by previous researchers,the relationship between diabetes and tendinosis is grad-ually clear.Conclusion As a systemic metabolic disease,diabetes can induce the occurrence of tendinosis or aggravate the pro-gress of tendinosis through a variety of ways and mechanisms.Research and clarification of these ways can provide us with a pow-erful weapon to study and treat tendinosis.However,at present,there are many possible pathogenesis of diabetes tendinosis,which still needs to be studied step by step to further clarify its main pathogenesis.

BACKGROUND: As one of the early discovered long non-coding RNAs (lncRNA), taurine upregulation gene 1 ( TUG1 ) has been widely expressed in a variety of tumors. Moreover, it promotes cell proliferation, differentiation, apoptosis, and migration. However, our understanding of its importance in the pathogenesis of cataracts remains limited. This study aimed to explore the mechanism by which lncRNA TUG1 mediates lens epithelial cell apoptosis in age-related cataracts (ARC) by regulating the microRNAs (miR-29b)/second mitochondria-derived activator of caspases axis, and to identify more non-surgical strategies for cataract treatment. METHODS: The messenger RNA expression levels of TUG1 , miR-29b, and Smac were detected using quantitative real-time polymerase chain reaction in vivo and in vitro . The expression of the Smac protein was analyzed by Western blotting and immunofluorescence. Flow cytometry and cell counting kit-8 assays were used to detect the cell apoptosis and proliferation rates, respectively. The targeted regulatory relationship between lncRNA TUG1 , miR-29b, and Smac was verified by viral vector construction, co-transfection, nuclear and cytoplasmic separation, luciferase reporter assays, and RNA immunoprecipitation. RESULTS: TUG1 and Smac were expressed at high levels in ARC and HLE-B3 cells treated with 200 μmol/L H 2 O 2 , whereas miR-29b expression was decreased. In vitro cell experiments confirmed that down-regulation of TUG1 could inhibit the apoptosis of lens epithelial cells. Mechanistically, Smac expression was negatively regulated by miR-29b. TUG1 competitively inhibited miR-29b expression and caused greater release of Smac. In addition, miR-29b partially reversed the effects of TUG1 on human lens epithelial cell line cells. CONCLUSIONS lncRNA TUG1 increases Smac expression and promotes apoptosis of lens epithelial cells in ARC by competitively inhibiting miR-29b. This mechanism is the cytological basis for ARC formation. Based on these results, the lncRNA TUG1/miR29b/Smac axis may be a new molecular pathway that regulates ARC development.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.
Humans ; Bacteria/genetics* ; Gene Editing ; Metabolic Diseases/therapy*

Autism spectrum disorder is a set of neurodevelopmental disorders with unclear etiology and pathogenesis and no cure. Studies have found that the gut microbiota plays a vital role in the occurrence and development of autism spectrum disorder. By supplementing with probiotics, diet management or fecal microbial transplantation, the balance of gut microbiota can be adjusted to improve the behaviors and symptoms of patients with autism spectrum disorder. This article reviews from the perspective of regulating the balance of gut microbiota to treat autism spectrum disorder, and aims to provide assistance for the research and treatment of autism spectrum disorder.

Objective:To compare the application effectiveness of conventional rehabilitation combined with thoracic spine mobility exercises and conventional rehabilitation in postoperative rehabilitation of patients with rotator cuff injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 204 patients with rotator cuff injury admitted to First Affiliated Hospital of Jinan University from February 2019 to February 2022, including 88 males and 116 females; aged 18-87 years [(54.1±11.8)years]. Initial unilateral arthroscopic rotator cuff repair was performed on all the patients. A total of 98 patients received a conventional rehabilitation plan (conventional rehabilitation group), and 106 patients received additional thoracic spine mobility exercises as well as conventional rehabilitation (additional exercise rehabilitation group). The visual analog scale (VAS), Constant shoulder joint score, University of California at Los Angeles (UCLA) shoulder joint score, and shoulder range of motion (forward flexion, abduction, and external rotation) before surgery and at 1, 3, and 6 months after surgery were compared between the two groups. The occurrence of complications after rehabilitation was observed.Results:All the patients were followed up for 6-18 months [(8.4±3.5)months]. The VAS score, Constant shoulder joint score, UCLA shoulder joint score, and shoulder joint range of motion of both groups were improved significantly at 1, 3, and 6 months after surgery compared with those before surgery (all P<0.01). There was no statistically significant difference in VAS score between the two groups before surgery and at 1, 3, and 6 months after surgery respectively (all P>0.05). At 3 and 6 months after surgery, the values of the Constant shoulder joint score of the additional exercise rehabilitation group were (77.7±5.8)points and (88.4±7.7)points respectively, which were higher than those of the conventional rehabilitation group [(73.7±6.6)points and (85.5±4.9)points] (all P<0.01). There was no statistically significant difference in the Constant shoulder joint score between the two groups before and at 1 month after surgery (all P>0.05). At 3 months after surgery, the value of the UCLA shoulder joint score of the additional exercise rehabilitation group was (25.5±3.7)points, significantly higher than that of the conventional rehabilitation group [(21.8±5.6)points] ( P<0.01). There was no statistically significant difference in the UCLA shoulder joint score between the two groups before surgery and at 1 and 6 months after surgery (all P>0.05). At 3 and 6 months after surgery, the forward flexion angles of the additional exercise rehabilitation group were (135.5±12.8)° and (165.1±11.3)° respectively, which were higher than those of the conventional rehabilitation group [(129.3±12.3)° and (151.1±11.2)°]; the abduction angles of the additional exercise rehabilitation group were (102.3±12.9)° and (130.4±15.1)° respectively, which were higher than those of the conventional rehabilitation group [(93.2±11.0)° and (123.5±13.7)°]; the external rotation angles of the additional exercise rehabilitation group were (57.2±13.1)° and (72.3±12.3)°respectively, which were higher than those of the conventional rehabilitation group [(46.4±8.8)° and (67.4±14.1)°] (all P<0.01). There was no statistically significant difference in the forward flexion, abduction and external rotation angles between the two groups before surgery and at 1 month after surgery (all P>0.05). At 6 months after surgery, recurrent rotator cuff tear occurred in 1 patient (1.0%) in the conventional rehabilitation group and in 2 (1.9%) in the additional exercise rehabilitation group; shoulder joint adhesion deveplpoed in 5 patients (5.1%) in the conventional rehabilitation group and in 3 (2.8%) in the additional exercise rehabilitation group. No statistically significant difference was found in the incidence rate of postoperative complications between the two groups (all P>0.05). Conclusion:Compared with the conventional rehabilitation plan, addition of thoracic spine mobility exercise to the rehabilitation after arthroscopic repair surgery in patients with rotator cuff injury can achieve better joint function and range of motion, with no increase in the incidence of complications.

Objective:To assess the effectiveness of Vision Therapy System 4 (VTS4) combined with traditional comprehensive training for ametropic amblyopia.Methods:A non-randomized controlled clinical study was performed.A total of 168 children aged 4-10 years with ametropic amblyopia were enrolled in The First Affiliated Hospital of Zhengzhou University from January 2018 to March 2021.The children were assigned to conventional comprehensive training combined with Vision Therapy System 4 group (conventional+ VTS4 group) and conventional group according to the preference of their guardian.Patients in conventional+ VTS4 group (84 children) received conventional comprehensive training combined VTS4 and patients in conventional group (84 children) were treated with conventional comprehensive training only, and the intervention was continuously used for over a year.Best corrected visual acuity (BCVA) of the patients converted to the logarithm of the minimum angle of resolution (LogMAR) units was examined by international standard visual acuity chart before and after therapy.Spherical equivalent of the patients was detected by optometry under cycloplegic conditions and skiascopy.Binocular and fusion vision was examined with a synoptiscope.The stereopsis was evaluated using Titmus Stereogram.The ocular axial length (AL) and mean keratometry (Km) were measured with the IOLMaster 500.The basic cure rate, BCVA, reconstruction rate of stereopsis, △SE, △AL and △Km following training were compared to evaluate the effectiveness and myopic shift between two groups.The patients in conventional+ VTS4 group were divided into 4-5 years old group and 6-10 years old group, with 42 cases in each group, and the basic cure rate, BCVA, reconstruction rate of stereopsis were compared to evaluate the therapeutic effect between the two groups.The basic cure was defined as acuity improved to ≥0.9, with reduced myopic diopter and stable therapy outcome over 6 months.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-0891-002). Written informed consent was obtained from guardians prior to any medical examination.Results:The basic cure rate of conventional+ VTS4 group was 58.33%(49/84), which was significantly higher than 40.48%(34/84) of conventional group ( χ2=5.358, P=0.021). The BCVA in the conventional+ VTS4 group was better than that in conventional group, showing a statistically significant difference ( Z=-2.537, P=0.011). The recovery rates of binocular vision, fusion vision and stereo vision were 87.93%(51/58), 78.33%(47/60) and 70.77%(46/65) in conventional+ VTS4 group, which were higher than 65.57%(40/61), 57.81%(37/64) and 52.86%(37/70) in conventional group, respectively, with significant differences between them ( χ2=8.259, 5.968, 4.566; all at P<0.05). No significant difference was found in △SE, △AL, and △Km between conventional group and conventional+ VTS4 group (all at P>0.05). The basic cure rate was 69.05%(29/42) in the children aged 4-5 years group, which was higher than 47.62%(20/42) in 6-10 years group, respectively, showing a significant difference ( χ2=3.967, P=0.046). Both BCVA and the stereo vision recovery rate in the 4-5 years old group were better than those in the 6-10 years old group ( Z=-2.046, P=0.041; χ2=4.624, P=0.032). Conclusions:A combination therapy of VTS4 and conventional comprehensive training can improve the visual acuity and reconstruct the fusion and stereopsis of children with ametropic amblyopia, without causing additional myopic drift.

Objective:To summarize and compare the characteristics of oral microbiota in women during the preconception period and the third trimester.Methods:This retrospective cohort study involved 55 women who were recruited in the Preconceptional Offspring Trajectory Study (PLOTS) conducted by Fudan University and followed up to the third trimester in the Maternal and Child Health Care Hospital of Jiading District of Shanghai from September 2016 to December 2019. A total of 110 unstimulated saliva samples were collected in the preconception period ( n=55) and the third trimester ( n=55). Features of oral microbiota in the samples were analyzed by 16S rRNA gene-based sequencing. Moreover, the related factors were also analyzed. Paired t test or Wilcoxon matched-pairs signed-ranks test were used to analyze the differences in α-diversity during preconception and the third trimester; t test, analysis of variance (ANOVA), Kruskal-Wallis test and Mann-Whitney U test for comparison between groups with different characteristics and permutational multivariate analysis of variance (PerMANOVA) for β-diversity were used; Linear discriminant analysis (LDA) effect size (LEfSe 1.0) was used to identify the iconic oral flora. Results:(1) The Ace index of oral microbiota was significantly lower in the third trimester than that in the preconception period [661.14(578.15-752.85) vs 730.64 (632.40-911.00), T=1 077.00, P=0.010]. There was also a significance difference in β-diversity ( F=12.539, R2=0.104, P=0.001). Some species such as Saccharibacteria_TM7_G3, Prevotella_7, Absconditabacteria_SR1_G1, Porphyromonas, Ruminococcaceae_UCG_014, Prevotella, Peptostreptococcus, Prevotella_2, Alloprevotella, Parvimonas, Solobacterium and Eubacterium_nodatum_group in saliva were statistically more abundant in the third trimester than those in the preconception period (all P<0.05). (2) The third-trimester Shannon index was lower among those with lower income [5.44 (5.08-5.77) vs 5.75 (5.44-6.12), U=219.00, P=0.029] and those with gargle habit after meal or dessert [5.36 (4.91-5.48) vs 5.72 (5.44-6.05), U=374.00, P=0.046]. Conclusions:The features of oral microbiota vary in women during the preconception period and the third trimester. There is a significant increase in the abundance of oral pathogenic and opportunistic bacteria in the third trimester.