AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.