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 investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

Objective To analyze the risk factors associated with the occurrence of rectal neuroendocrine tumors (RNETs) and construct a risk prediction model. Methods Clinical data of patients who underwent electronic colonoscopy were collected. The clinical information on patients with and without RNETs were compared, and potential risk factors for RNETs were identified. Binary logistic regression was performed to analyze the relevant risk factors and construct a risk prediction model. Results Among 164 patients, 66 were diagnosed with RNETs, and 98 who did not have such a condition were randomly selected. Univariate logistic regression analysis revealed that age, fatty liver, anxiety and depression, total cholesterol, triglyceride levels, and carcinoembryonic antigen (CEA) were significant factors influencing the occurrence of RNETs (P<0.05). Multivariate logistic regression analysis identified age (P=0.015), anxiety and depression (P=0.031), cholesterol level (P=0.009), fatty liver (P=0.001), and CEA (P<0.001) as independent risk factors for RNETs. The participants were randomly divided into training and test sets at a 7:3 ratio. The training set was used to construct a nomogram-based risk prediction model, and the testing set was used for internal validation. The area under the curve values for the training and testing sets were 0.843 and 0.772, respectively (P>0.05). These findings indicate a good discriminative performance. The calibration curves for the training and testing sets were in good agreement with the 45° standard line, which suggests that the predicted probabilities were consistent with the actual outcomes. Decision curve analysis showed that the model provided a high net benefit within a threshold range of 0.2 to 0.7 for clinical decision making. Conclusion Young age, fatty liver, high CEA levels, high cholesterol levels, and anxiety and depression are independent risk factors for RNETs. The nomogram model constructed based on these risk factors exhibits a strong capability to predict the occurrence of RNETs, and clinical intervention can be considered based on the predicted probability values.

To implement the instructions and directives of General Secretary Xi Jinping on important documents related to traditional Chinese medicine （TCM）， adhere to the equal emphasis on TCM and Western medicine， and promote mutual complementarity， win-win cooperation， and coordinated development between TCM and Western medicine， the China Association of Chinese Medicine has organized seminars on the clinical dominant diseases of TCM in multiple professional fields， achieving a series of results. The aim is to implement the research on dominant diseases of TCM described in the Law of the People's Republic of China on Traditional Chinese Medicine and the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance， Innovation and Development of Traditional Chinese Medicine， thus serving the construction of advantageous specialties， clinical talent cultivation， national scientific and technological layout， and academic innovation leadership. In the field of otolaryngology， the China Association of Chinese Medicine and many Chinese and Western medicine experts across the country have conducted multiple in-depth discussions and research. At the 10^th Clinical Dominant Disease Series Youth Salon， they have elaborated and demonstrated the basic and specific suggestions and consensus on the clinical advantages of TCM and integrated TCM and Western medicine in the treatment of allergic rhinitis （AR）， making great progress. However， there is still a lack of detailed research paths. Under the guidance of the China Association of Chinese Medicine and based on the TCM Dominant Disease Series Salon for AR， this study analyzed the difficulties encountered in AR diagnosis and treatment according to the occurrence and development law of AR. Based on the advantages and characteristics of AR diagnosis and treatment by TCM and integrated TCM and Western medicine， it explored the research paradigm and technological layout points of AR and put forward suggestions. The layout involved four aspects： Optimization of the AR diagnosis and treatment system， prevention and control of comorbidities， management of chronic diseases， and a platform for TCM inheritance. Additionally， suggestions for layout and research directions， expected goals and values， and priority levels for funding were proposed. The study is expected to provide a theoretical basis and development ideas for the future prevention and treatment of AR with TCM and integrated TCM and Western medicine and promote the high-quality development of TCM.

Objective    To investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. Methods    Forty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+ 1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. Results    There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. Conclusion    The combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.

Nonalcoholic fatty liver disease(NAFLD),also known as metabolic associated fatty liver disease(MAFLD),is one of the most common chronic liver diseases characterized by the fat accumulation in the liver and hepatocellular damage.Patients with NAFLD can manifest as simple fatty liver or non-alcoholic steatohepatitis(NASH)in the early stage,and can progress to hepatic fibrosis,hepatic cirrhosis,hepatic fail-ure,and hepatic carcinoma in the late stage.NAFLD has become the most common chronic liver disease,af-fecting more than 30%of the population worldwide,posing a threat to human health that cannot be ignored.However,the current research on NAFLD is still incomplete,and there is no ideal medication for the treat-ment of NAFLD.The clinical management of NAFLD lacks unified standards and evidence-based evidence,and the multiple comorbidities bring challenges to the clinical management of NAFLD.This article was aimed to review the research progress in the clinical management of NAFLD,including the diagnosis and non-invasive examination methods,evaluation and commonly used tools,treatments methods,advantages and disadvanta-ges,so as to provide a reference for the clinical management of NAFLD.

Objective:To investigate the influencing factors of increased tube bleeding within 24 h after coronary artery bypass grafting(CABG) and its correlation with perioperative complications.Methods:This study was a prospective observational study. The patients with CABG surgery were enrolled in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2021. The age, sex, complications, blood tests and other clinical data of outpatients were collected. Left ventricular ejection fraction(EF) and left ventricular enddiastolic diameter(LVED) were detected by echocardiography. MGF and PI of grafts were recorded during CABG. Perioperative troponin Ⅰ, blood clotting pentathlon, all-cause death, perioperative myocardial fraction, atrial fibrillation and stroke were collected. According to the tube bleeding within 24 h after operation, the patients were divided into increased group(tube bleeding>1 000 ml) and normal group(tube bleeding≤1 000 ml). The preoperative baseline data, intraoperative indexes and perioperative complications were compared between the two groups. Logistic regression, Spearman and linear regression models were used to analyze the correlation between tube bleeding within 24 h and clinical data.Results:304 patients underwent CABG were enrolled. There were 185 cases(60.9%) in the increased group and 119 cases(39.1%) in the normal group. After adjusting for age, sex and BMI, multivariate logistic regression analysis showed that male( OR=2.40, 95% CI: 1.38-4.18, P=0.002), history of stroke( OR=2.37, 95% CI: 1.07-5.26, P=0.034), and history of myocardial infarction( OR=1.81, 95% CI: 1.13-2.91, P=0.014) could significantly increase the risk of tube bleeding within 24 h after surgery. The average blood flow of the anterior descending branch( OR=0.99, 95% CI: 0.99-1.00, P=0.022) and the circumflex branch( OR=0.99, 95% CI: 0.98-1.00, P=0.003) during the operation was significantly negatively correlated with the increase of tube bleeding within 24 h after surgery, while the PI of anterior descending branch( OR=1.81, 95% CI: 1.26-2.61, P=0.001), circumflex branch( OR=1.45, 95% CI: 1.07-1.97, P=0.017), right coronary artery( OR=1.84, 95% CI: 1.29-2.62, P=0.001) were positively correlated with the increase of tube bleeding within 24 h after operation. In addition, prothrombin time significantly increased the risk of increased tube bleeding within 24 h after surgery( OR=1.16, 95% CI: 1.03-1.30, P=0.018). Linear regression analysis showed that there was a significant positive linear correlation between ICU time and tube bleeding within 24 h after surgery( OR=0.17, 95% CI: 0.96-4.58, P=0.003), and a significant negative linear correlation between postoperative ejection fraction and tube bleeding within 24 h( OR=-0.25, 95% CI: -33.18--13.07, P<0.001). Conclusion:Increased tube bleeding within 24 h after CABG is most common in males and patients with a history of cardiovascular and cerebrovascular infarction. Better graft hemodynamic parameters can reduce the tube bleeding within 24 h after the operation, further improve cardiac function and reduce ICU time.

Objective:To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer.Methods:This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results:The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference ( P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion:Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.