AIM: To analyze the current status, research hotspots, and development trends of international studies on ocular surface microbiota based on bibliometrics.METHODS: Leveraging the Web of Science database, we conducted a targeted literature search on ocular surface flora. The retrieved data were meticulously screened and weighted to enhance relevance. The bibliometric analysis delved into publication trends, authorship patterns, institutional collaborations, and pivotal research themes. Employing Cite Space software, we visually dissected the landscape of institutional and national partnerships, citation impact, keyword co-occurrences, keyword clustering dynamics, and the emergence of new research trends.RESULTS: A total of 3 884 publications were ultimately included, with an overall upward trend in the number of publications in the field of ocular surface microbiota from 2003 to 2023, with the most rapid growth occurring from 2019 to 2022. The top three regions/countries by publication volume are the United States(1 039 papers), China(570 papers), and India(302 papers). The top three authors by publication volume are Willcox Mark(48 papers), Sharma Savitri(33 papers), and Fleiszig Suzanne M.J(27 papers). The top three institutions by publication volume, all from the United States, are the University of California, L.V. Prasad Eye Institute, and Harvard University. The citation network map of the literature includes 801 nodes and 1 508 connections, with the most frequently cited document being Temporal Stability and Composition of the Ocular Surface Microbiome. The top 5 keywords by frequency of occurrence are, in order, keratitis, bacterial flora, identification, inflammation, and endophthalmitis. The keyword clustering analysis yielded a total of 8 clusters, which are specifically reflected in three aspects: ocular-related diseases, the relationship between ocular surface microbiota and ocular surface structures, and detection methods for ocular surface microbiota. The keyword with the highest burst strength is ciprofloxacin. Keywords that have emerged in recent years and continue to the present include diversity, gut microbiome, and ocular surface microbiome.CONCLUSION: Currently, the study of ocular surface microflora is gaining momentum globally, with a particular focus on the diversity of microflora, the composition of the core microbiome, and its impact on ocular diseases. In the future, research should concentrate on elucidating the functional metabolism of the ocular surface microflora and further investigate the causality and mechanisms by which changes in the ocular surface microflora are related to diseases.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group， acupuncture group， non-acupoint group， and donepezi group， with 10 mice in each group， and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui （GV 20）， Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17）. Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17） were stimulated on the left side first and then on the right side alternately， once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian， non-acupoint points under the ribs， once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment， Morris water maze tests （to record orientation sailing latency， number of traverses through the platform quadrant） and open field （to record distance travelled） were used to evaluate learning and memory abilities； hippocampal neuronal damage was analyzed via HE and Nissl staining； mitochondrial membrane potential and reactive oxygen species （ROS） were measured using assay kits； Western blot and qRT-PCR were performed to detect silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor gamma coactivator 1-alpha （PGC-1α）， and mRNA expression levels. ResultsCompared with the normal group， mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues， and reduced number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-staining-positive cells in the hippocampal tissues， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1， PGC-1α （P＜0.01）； HE staining showed that the hippocampal tissues of the mice was loosely arranged， with reduced number of neurons and vacuolar degeneration； Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged， and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group， mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue， higher number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-stained positive cells in the hippocampal tissue， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1 and PGC-1α （P＜0.01）， and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group， the orientation sailing latency shortened in the acupuncture group of mice （P＜0.01）. ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function， thus alleviating the neuronal damage， which is one of the possible mechanisms for its treatment of Alzheimer's disease.

ObjectiveTo evaluate the application of prostate-specific membrane antigen （PSMA）PET/CT in prostate biopsy screening， and propose effective strategies for prostate biopsy decision making based on PSMA PET/CT detection. MethodsA retrospective analysis was conducted on PSMA PET/CT imaging and clinical pathological data from 155 patients with suspected prostate cancer between January 2020 and December 2023. PRIMARY score was used as the standardized evaluation method for PSMA PET/CT in the diagnosis of prostate cancer. And compared the positive prostate biopsy rates， missed diagnosis rates and biopsy reduction rates were compared regarding different PRIMARY scores. Receiver operating characteristic （ROC） curves were used to analyze prostate-specific antigen （PSA） and its derived parameters and identify the most suitable supplementary screening indicators for combined use with the PRIMARY score. ResultsAmong patients with PRIMARY scores of 1 to 5， the proportions of patients diagnosed with prostate cancer were 15.8% （3/19）， 17.1% （7/41）， 50% （12/24）， 95.2% （20/21） and 98% （49/50）， respectively. Using PRIMARY score of 3-5 as the biopsy screening strategy resulted in a positive prostate biopsy rate of 85.3% and biopsy reduction rate of 38.7%， but a missed diagnosis rate of 11%. PSA density > 0.15 ng/（mL·cm³） was selected as a supplementary screening criterion to detect prostate cancer from patients with PRIMARY scores of 1-2. The combined application of the above two screening criteria reduced the missed diagnosis rate to 2.2%. ConclusionThis study proposes a novel biopsy screening strategy for suspected prostate cancer patients using PSMA PET/CT， that is， a PRIMARY score of 3-5 or a PRIMARY score of 1-2 but PSA density>0.15 ng/（mL·cm³）， which can effectively avoid unnecessary biopsies and significantly reduce the missed diagnosis rate.

ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

Objective: To explore relationship of sleep quality with overweight and obesity among middle school students, so as to provide a reference basis for improving adolescent sleep health. Methods: From September to December 2023, 5 713 middle school students aged 13 to 18 were selected by stratified cluster random sampling method in six regions, including Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi. Sleep quality survey was conducted on middle school students by Pittsburgh Sleep Quality Index. Height and weight were measured, and World Health Organization s standards for growth and development of children and adolescents was used to evaluate their nutritional status. Both χ 2 test and Logistic regression analysis were used to analyze the association between sleep quality and nutritional status of middle school students. Results: The non compliance detection rate of sleep quality was 38.4% among girls, but 29.2% among boys, and the difference was of statistical significance( χ 2=54.08, P < 0.01 ). The detection rate of substandard sleep quality was 34.2% in the group with normal nutritional status, 38.3% in the group with overweight, 43.7% in the group with obesity and 26.0% in the group with emaciation, and the difference in the rates of substandard sleep quality among middle school students of different nutritional status was statistically significant ( χ 2=68.15, P <0.01). Logistic regression analysis showed that, after controlling for mental health and physical activity, the detection rate of substandard sleep quality in the obese groups was 1.30 times higher than that in the normal group, respectively( OR =1.30, 95% CI =1.06- 1.59 , P <0.01). Conclusions Sleep quality is correlated with overweight and obesity among middle school students, and there are gender differences. Intervention policies should be formulated according to the characteristics of different genders.

Objective: To explore the association between physical activity and sleep quality among middle school students, so as to provide reference for adolescent sleep improvement. Methods: From September to December 2023, 5 713 middle school students aged 13-18 years were selected from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi by stratified cluster random sampling method. Pittsburgh Sleep Quality Index (PSQI) and Evaluation of Physical Activity Levels of Children and Adolescents Aged 7-18 Years were used to investigate and evaluate sleep quality and physical activity. Comparisons between groups were made using the t-test, Mann-Whitney U-test, and associations between physical activity and sleep quality of middle school students were analyzed using Spearman correlation and linear regression methods. Results: The total PSQI scores were 4.0(2.0,6.0) and 5.0 (3.0,6.0) for boys and girls, respectively, with significant sex difference ( Z =-10.90, P <0.01); light physical activity(LPA) and moderate to vigorous physical activity(MVPA) of boys were 18.57 (2.86, 42.86) and 68.57 (35.71, 119.18)min, and girls were 14.29 (0.00, 30.00) and 55.71 (31.43, 92.86)min respectively, and the differences were statistically significant ( Z =3.65, -8.65 , P <0.01). The results of Spearman correlation regression showed that adolescents MVPA was negatively correlated with the total PSQI score ( r =-0.04, P <0.01). After controlling for variables such as mental health, nutritional status and maximum oxygen uptake, the results of linear regression analysis showed that PSQI total score negatively predicted MVPA among middle school students ( B =-4.76, 95% CI =-7.16 to -2.36, P <0.05). Conclusion The longer the duration of physical activity among middle school students, the better the quality of sleep.

ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.

Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

Aging is a natural process in which tissue and organ function declines as organisms age. Aging is the inevitable outcome of the organism and is irreversible. The aging process is accompanied by degenerative changes in the morphological structure of multiple organs of the body, leading to an increase in the incidence of chronic diseases such as hypertension, cardiovascular and cerebrovascular diseases, hyperlipidemia, and diabetes year by year. In recent years, natural phytochemicals have attracted widespread attention from the public due to their advantages such as non-toxicity or low toxicity, low cost, and various biological activities. Epigallocatechin gallate (EGCG) is a dietary polyphenol extracted from green tea, which has a variety of biological functions including anti-oxidation, anti-inflammation, hypoglycemic, hypolipidemic and anti-aging activities. The EGCG-mediated anti-aging mechanism has been investigated in many studies with different aging models. This article reviews the research progress on rodents, nematodes, fruit flies, and cell aging models, focusing on summarizing the lifespan extension and physiological changes of rodents, nematodes and fruit flies after EGCG intervention from multiple angles, and exploring potential mechanism by which EGCG delays aging and extends lifespan. This review provides a theoretical reference for the study of the anti-aging mechanism of phytochemicals.