ObjectiveThis paper aims to study the potential active compound components and action mechanism of Shenqi Dihuangtang in the treatment of diabetic kidney disease （DKD） through network pharmacology and in vivo experimental verification. MethodsUltra-high-performance liquid chromatography-Q-exactive orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS） technology was used to clarify the main active chemical components of Shenqi Dihuangtang， and it was combined with network pharmacology methods such as gene ontology （GO） functional annotations and Kyoto encyclopedia of genes and genome （KEGG） to predict the potential action mechanism of Shenqi Dihuangtang in treating DKD. Subsequently， the DKD model of db/db male mice was established， and the mice were randomly divided into model group， low-dose Shenqi Dihuangtang group （6.10 g·kg^-1）， medium-dose Shenqi Dihuangtang group （12.19 g·kg^-1）， high-dose Shenqi Dihuangtang group （24.38 g·kg^-1）， and daplizin group （1.25 mg·kg^-1）. During the same period， C57BL/6J male mice were selected into normal group and received drug intervention for 8 weeks， respectively. During this period， the body weight and fasting blood glucose （FBG） of the mice were dynamically monitored， and oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed at the end of dosing. The levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， uric acid （UA）， albumin （ALB）， and total protein （TP） were measured by an automatic biochemical analyzer， and 24-hour urine protein was measured by a urine protein quantitative kit. Hematoxylin-eosin （HE）， periodic-acid Schiff （PAS）， and Masson staining were employed to observe the renal histopathology. The expression of nephrotic protein Nephrin was observed by immunohistochemistry. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins such as TGF-β₁， Smad2/3， α-smooth muscle actin （α-SMA）， neural-cadherin （N-Cadherin）， and snail protein. ResultsUPLC-Q-Exactive Orbitrap MS identified 384 active compounds in the aqueous extract of Shenqi Dihuangtang. According to oral bioavailability≥30% and the five drug-like principles， 44 key active ingredients were screened out， and 169 intersection targets highly correlated with DKD were matched. Among them， there was a significant interaction relationship between tumor necrosis factor（TNF）， interleukin（IL）-6， protein kinase B（Akt）1， Caspase-3， Jun proto-oncogene （JUN）， hypoxia inducible factor-1α（HIF-1α）， B cell lymphoma-2（Bcl-2）， matrix metallopeptidase-9（MMP-9）， IL-1β， and TGF-β₁. GO functional annotations were significantly enriched in cellular components such as membrane rafts， membrane microdomains， and collagen-containing extracellular matrix， molecular functions such as DNA-binding transcription factor binding， R-Smad binding， and Smad protein binding， as well as biological processes such as reactions to lipopolysaccharides（LPS）， reactions to bacteria-derived molecules， and wound healing. The KEGG pathway was significantly enriched in lipids and atherosclerosis， TGF-β signaling pathway， phosphatidylinositol 3 kinase （PI3K）/Akt signaling pathway， etc. In vivo experimental results showed that the high-dose Shenqi Dihuangtang group could significantly reduce FBG levels in db/db mice （P<0.01）， improve OGTT （P<0.01） and ITT （P<0.01） levels， reduce SCr （P<0.01）， BUN （P<0.01）， UA （P<0.01） and 24-hour BUN （P<0.01）， and increase ALB （P<0.01） and TP （P<0.01） levels. Pathological staining confirmed that the high-dose Shenqi Dihuangtang group could significantly reduce the glomerular mesangial matrix area and collagen deposition （P<0.01） and upregulate the positive expression rate of Nephrin （P<0.01）. Western blot results showed that the high-dose Shenqi Dihuangtang group significantly downregulated the expression of TGF-β₁ （P<0.01） and Smad2/3 （P<0.01） signal molecules and inhibited the protein levels of α-SMA （P<0.01）， N-Cadherin （P<0.01）， and Snail （P<0.01）. ConclusionShenqi Dihuangtang can inhibit the TGF-β₁/Smad signaling axis and block the renal EMT process， thereby improving DKD renal fibrosis damage. Further analysis of its key active components and clinical transformation pathways is needed in the future.

Objective: To explore the association of outdoor activity time and sleep duration with screening myopia in primary school students, so as to provide strategies for myopia prevention. Methods: Through a convenience sampling method, a survey was conducted among 4 248 primary school students aged 7-13 years from three primary schools in Xihu District, Nanchang City, Jiangxi Province from May to July, 2023. The average daily outdoor activity time and sleep duration on both weekdays and weekends were investigated in primary school students by using a self designed questionnaire. Uncorrected visual acuity tests and non cycloplegic autorefraction were measured by professional optometrists. Inter group comparisons were conducted using the Chi square test. Logistic regression model was used to analyze the association of outdoor activity time and sleep duration with screening myopia. Results: The detection rate of screening myopia in primary school students was 33.6%, with the rate in boys (32.0%) lower than that in girls (35.3%), and the difference was statistically significant ( χ 2=5.11, P =0.02). The analysis results of Logistic regression showed that after adjusting for factors such as gender, grade and parental education level, both average daily outdoor activity time ＜2 h on both weekdays and weekends ( OR =1.27, 95% CI =1.11-1.46) and sleep duration <10 h ( OR =1.17, 95% CI =1.01- 1.35 ), as well as their combined effect ( OR =1.57, 95% CI =1.25-1.98), were associated with an increased risk of screening myopia in primary school students(all P <0.05). Subgroup analysis results indicated that compared to boys ( OR =1.46, 95% CI = 1.07 -1.99), girls( OR =1.73, 95% CI =1.22-2.44) with insufficient outdoor activity time and sleep duration had a higher risk of screening myopia(both P <0.05). Conclusions There is a negative correlation of outdoor activity time and sleep duration with screening myopia in primary school students. Outdoor activity time and extending sleep duration should be increased to reduce the risk of myopia in primary school students.

Objective: To investigate the serological identification and blood group gene sequencing analysis of two rare cases of K phenotype producing high-frequency antigen antibodies (anti-Ku), and to study the serological interrelationship between K cells and the high-frequency antigen antibody anti-KL. Methods: Serological methods were used to identify the antigen phenotypes of the ABO, Rh, and Kell blood group systems and to screen for and identify unexpected antibodies in the two patients. The characteristics of the unexpected antibodies were verified by the indirect antiglobulin test (IAT) using papain or dithiothreitol (DTT) -treated screening cells. The titer of anti-Ku was determined via the tube method using DTT-treated plasma. The Kell blood group genotype was determined by gene sequencing. The distinctive antigenicity of K cells was validated through their reactivity with anti-KL in IAT, and absorption-elution techniques were employed to corroborate the type of anti-KL. Results: Serological findings: Case 1 was blood group O, CCDee; Case 2 was blood group A, CCDee. Both cases exhibited the Kell phenotype: K-k-, Kp (a-b-). High-frequency antigen antibodies were detected in the plasma of both patients. The reactivity of these antibodies was slightly enhanced with papain-treated screening cells but became negative with DTT-treated cells. The anti-Ku (IgG) titer for Case 1 was 64. For Case 2, the anti-Ku (IgM) titer was<1, and the anti-Ku (IgG) titer was 32. Gene sequencing revealed that both cases harbored a homozygous c.715G>T mutation in the KEL gene, corresponding to the genotype KEL02N.24, consistent with the rare K phenotype. The unique high expression of the Kx antigen on K cells was confirmed through the antibody characteristics of anti-KL. Absorption-elution techniques demonstrated that K cells could separate anti-Km and anti-Kx, thereby supporting the classification of anti-KL. Conclusion: Serological and molecular biological assays identified both patients as having the rare Kell-null (K ) phenotype. If such rare blood types go undetected in transfusion medicine, the administration of standard blood products can readily induce the production of high-frequency antigen antibodies such as anti-Ku, potentially leading to a transfusion crisis due to the subsequent difficulty in finding compatible blood. The serological relationship between K cells and anti-KL clarified the characteristic high expression of the Kx antigen on K phenotype erythrocytes and concurrently supported the typological features of the rare high-frequency antibody anti-KL. This represents the first such verified report in China.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

Based on the holistic concept of the integration of body and mind， this paper systematically elucidates the movement characteristics， mechanisms of action， and rehabilitative effects of the integrated regulation of body and mind in traditional exercise therapy from the three core dimensions of regulating the body， regulating qi， and regulating the mind. Its movement are characterized by mind-guided movements integrating reflection and qi， relaxed and resilient movements of both body and mind， balanced movements integrating deficiency and excess while maintaining balanced body-mind alignment， and slow movements combining motion with stillness. The underlying mechanisms involve externally mobilizing the limbs while internally regulating the zang-fu （脏腑） organs， dredging the meridians， connecting the interior and exterior， promoting the integrated regulation of body， qi， and mind， and coordinating the interaction between body and mind to regulate overall physiological function， thereby improving cognitive， motor， cardiopulmonary， and other functional outcomes during rehabilitation.

ObjectiveTo observe the mechanism through which Qige San inhibits tumor angiogenesis in esophageal cancer （EC） by regulating the microRNA-133a （miR-133a）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsCell experiments were conducted by transfecting miR-133a mimics through liposomes and utilizing PI3K/Akt signaling pathway inhibitors. The effects of 60 mg·L^-1 and 100 mg·L^-1 Qige San on inflammatory factor secretion in the supernatant of EC9706 cells （esophageal cancer cells） were observed. EC9706 cell supernatants were then extracted and used as conditioned media to treat human umbilical vein endothelial cells （HUVECs）. The effects of the conditioned media on the proliferation， migration， tube formation， and apoptosis of HUVECs were examined. Animal experiments involved establishing a subcutaneous tumor model in nude mice with EC9706 cells. After grouping and administration， tumor volumes were measured regularly. At the end of the experiment， tumors were harvested， and histopathological changes were observed under a microscope after hematoxylin-eosin （HE） staining. Real-time polymerase chain reaction （Real-time PCR） was adopted to measure miR-133a expression in the tumor tissue of each group， while Western blotting was employed to analyze the expression of key signaling molecules， such as phosphorylated Akt （p-Akt）， as well as endothelial cell markers， cluster of differentiation 31 （CD31） and cluster of differentiation 34 （CD34）， in the tumor tissue. ResultsCell experiments showed that compared with the blank group， the supernatant of EC9706 cells promoted tube formation of HUVECs （P<0.05）. Both low and high doses of Qige San inhibited tube formation of HUVECs （P<0.05）. All doses of Qige San， PI3K/Akt inhibitor， and the combination reduced the content of interleukin-6 （IL-6） （P<0.05）， while high-dose Qige San， inhibitor， and combination all reduced the content of interleukin-8 （IL-8） （P<0.05）. Compared with the EC9706 blank supernatant group， Qige San-conditioned medium inhibited the proliferation of HUVECs （P<0.05）. Qige San， the inhibitor， and the combination all inhibited the migration and tube formation （P<0.05） and increased the late apoptosis and total apoptosis rates of HUVECs （P<0.05）. In addition， the low-dose combination induced early apoptosis of EC9706 cells （P<0.05）. Compared with the blank supernatant group， the miR-133a mimic combined with Qige San synergistically reduced IL-6/IL-8 （P<0.05）， and enhanced the inhibition on proliferation， migration， and tube formation of HUVECs （P<0.05）. Animal experimental results showed that compared with the model group， both Qige San and cisplatin inhibited the growth of xenograft tumors in nude mice （P<0.05）， promoted tumor cell necrosis， and reduced capillary formation. High-dose Qige San upregulated miR-133a expression （P<0.05）. Moreover， compared with the model group， cisplatin， Qige San， and the combination all downregulated the expression of p-Akt， CD31， and CD34 （P<0.05）. ConclusionQige San upregulates miR-133a expression， inhibit PI3K/Akt signaling pathway activity， and improve the tumor inflammatory microenvironment to suppress the growth and tumor angiogenesis of HUVECs， thereby inhibiting esophageal cancer.

AIM: To investigate the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters in patients with hypertensive retinopathy(HRP).METHODS: A total of 50 patients(22 left eyes and 28 right eyes)with HRP admitted to our hospital from June 2021 to June 2023 were retrospectively included as the experimental group, and 50 healthy physical examination subjects(22 left eyes and 28 right eyes)during the same period were included as the healthy group. Pearson correlation was used to analyze the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters.RESULTS: The AUC values of fundus blood flow parameters and carotid artery ultrasound blood flow parameters and their combined diagnosis of HRP were 0.853, 0.844 and 0.935, respectively. Pearson correlation analysis showed that carotid systolic peak blood flow velocity was negatively correlated with foveal avascular zone(FAZ)area, FAZ circumference and non-circularity index, and positively correlated with macular vascular density(all P<0.05). The end-diastolic blood flow velocity was positively correlated with FAZ area and macular vascular density(all P<0.05). The internal carotid artery resistance index was positively correlated with FAZ area(P<0.05).CONCLUSION: The combination of fundus blood flow parameters and carotid artery ultrasound blood flow parameters in the diagnosis of HRP has good application value in the diagnosis of HRP.

Objective To investigate the relationship between umbilical cord blood regulated upon activa-tion normal T cell expressed and secreted(RANTES),cyclophilin A(CyPA)and neonatal brain injury(NBI)in neonates delivered by puerperant women with premature rupture of fetal membrane(PROM)and intrau-terine infection(IAI).Methods A total of 157 puerperant women with PROM and IAI who gave birth in the hospital from January 2022 to March 2024 were selected as the experimental group.Another 80 healthy partu-rients were selected as the control group.Neonates delivered by puerperant women with PROM and IAI were divided into NBI group(61 cases)and non-NBI group(96 cases)according to whether or not NBI occurred.The levels of RANTES and CyPA in umbilical cord blood were detected.NBI in neonates delivered by puerp-erant women with PROM and IAI was used as the dependent variable,and the influencing factors were deter-mined by multivariate Logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of umbilical cord blood RANTES and CyPA levels for NBI in neonates delivered by puerperant women with PROM and IAI.Results Compared with neonates delivered in control group,the levels of RANTES and CyPA in umbilical cord blood of neonates delivered in experimental group were in-creased,and the differences were statistically significant(P＜0.05).PROM type,1 min Apgar score,procalci-tonin(PCT),C-reactive protein,RANTES,CyPA were associated with NBI in the neonates delivered by puer-perant women with PROM and IAI(P＜0.05).The independent risk factors for NBI were increased Apgar score within 1 min(P＜0.05),and the independent protective factors were increased PCT,R ANTES and CyPA(P＜0.05).ROC curve analysis results showed that the area under the curve of umbilical cord blood RANTES and CyPA combined to predict the occurrence of NBI in neonates delivered by puerperant women with PROM and IAI was 0.874,which was larger than the 0.787 and 0.791 predicted by umbilical cord blood RANTES and CyPA alone(Z=3.248,2.801,P=0.001,0.005).Conclusion Umbilical cord blood RANTES and CyPA have high predictive efficacy for NBI in neonates delivered by puerperant women with PROM and IAI.

Objective To investigate the correlation between serum homeodomain interacting protein ki-nase 2(HIPK2),annexin A5(ANXA5)and coronary stenosis and prognosis in patients with acute myocardial infarction(AMI).Methods A total of 277 AMI patients who received interventional treatment in this hospi-tal from January 2021 to July 2023 were selected as the AMI group,and another 140 cases with normal or very mild stenosis in coronary angiography during the same period were selected as the control group.According to the degree of coronary artery stenosis(Gensini score),the AMI patients were divided into mild coronary arter-y stenosis group(86 cases),moderate coronary artery disease group(111 cases)and severe coronary artery disease group(80 cases).According to the prognosis,they were divided into poor prognosis group(80 cases)and good prognosis group(197 cases).Enzyme-linked immunosorbent assay was used to detect the serum HIPK2 and ANXA5 levels.Spearman correlation analysis was used to analyze the correlation between serum HIPK2 and ANXA5 levels and Gensini score in patients with AMI.Multivariate unconditional Logistic regres-sion was used to determine the relationship between serum HIPK2 and ANXA5 levels and prognosis of AMI patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficiency of serum HIPK2 and ANXA5 levels on prognosis of AMI patients.Results Compared with the control group,the ser-um HIPK2 level in the AMI group increased and the ANXA5 level decreased,and the differences were statisti-cally significant(P＜0.05).The serum HIPK2 levels in the mild coronary artery stenosis group,moderate coronary artery stenosis group and severe coronary artery stenosis group increased successively,while the ANXA5 levels decreased successively,and the differences were statistically significant(P＜0.05).Gensini score was positively correlated with serum HIPK2 level and negatively correlated with serum ANXA5 level in AMI patients(P＜0.05).The Gensini score of AMI patients was positively correlated with the serum HIPK2 level(r=0.785,P＜0.05),and negatively correlated with the serum ANXA5 level(r=-0.798,P＜0.05).Compared with the good prognosis group,the serum HIPK2 level in the poor prognosis group increased(P＜0.05),and the ANXA5 level decreased(P＜0.05).After adjusting for confounding factors,high HIPK2 was an independent risk factor for poor prognosis in AMI patients(P＜0.05),and high ANXA5 was an independ-ent protective factor(P＜0.05).The area under the curve of the combined prediction of serum HIPK2 and ANXA5 levels for the prognosis of AMI patients was 0.875,which was greater than 0.778 and 0.784 predic-ted by serum HIPK2 and ANXA5 levels alone(P＜0.05).Conclusion The serum HIPK2 level is increased and the ANXA5 level is decreased in patients with AMI,which is related to the aggravation of coronary steno-sis and the poor prognosis.The combination of serum HIPK2 and ANXA5 levels is more effective in predic-ting the prognosis of patients with AMI.

Objective:To systematically elucidate the molecular mechanism of hesperetin in the treatment of heart failure by network pharmacology, molecular docking, and molecular dynamics, and to clarify its key targets and pathway regulatory networks.Methods:Potential targets of hesperetin were retrieved from the PubChem, Pharmmapper, SwissTargetPrediction, and Similarity ensemble approach databases. Heart failure-related targets were obtained from the OMIM, GeneCards, and TTD databases. Intersection targets were identified using Venny 2.1. A protein-protein interaction (PPI) network of potential targets was constructed using the STRING database and Cytoscape 3.9.0 software. Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of key targets were performed using the Metascape database. Molecular docking was carried out using Autodock vina1.1.2. GROMACS (2024.03) was employed to conduct a 100 ns molecular dynamics simulation on the optimal affinity complex. The thermodynamic stability of the candidate complex during simulation was evaluated by analyzing the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and binding free energy. Data were analyzed by an independent sample t test or one-way analysis of variance. Results:A total of 356 related targets of hesperetin and 2 923 related targets of heart failure were screened, with 152 intersection targets identified as potential targets for hesperetin intervention in heart failure. PPI network topological analysis revealed key targets for hesperetin intervention in heart failure, including insulin-like growth factor 1, estrogen receptor 1 (ER1), cysteine aspartic acid specific protease-3, sarcoma proto-oncogene, matrix metalloproteinase 9 (MMP9), MMP2, Janus kinase 2 (JAK2), albumin, heat shock protein 90 alpha family class A member 1, epidermal growth factor receptor, and B-cell lymphoma-2 (Bcl-2). GO functional enrichment analysis indicated that biological processes were mainly enriched in response to hormone stimulation, positive regulation of cell migration, gland development, response to nutritional levels, regulation of system processes, and response to trauma. Molecular functions were primarily enriched in phosphotransferase activity, nuclear receptor activity, endopeptidase activity, kinase binding, heme binding, hormone binding and protease binding. Cellular components were mainly enriched in membrane-related structures such as vesicle cavity, membrane raft, vacuole cavity, receptor complex and extracellular matrix containing collagen. KEGG pathway enrichment analysis showed that these key targets were significantly enriched in lipid and atherosclerosis, diabetic cardiomyopathy, and the hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated that the binding energy of hesperetin to MMP9 (?46.442 kJ/mol) was significantly lower than that to other key targets. Molecular dynamics simulations revealed that the hesperetin-MMP9 complex maintained structural stability, with an average RMSD of 1.60 ?. The average RMSF values of MMP9 residues (0.83 ?) and ligand atoms (0.68 ?) indicated stable protein conformation and ligand-binding states. The Rg values of MMP9 [(15.04±0.60) ?] and hesperetin [(4.19±0.35) ?] showed minimal fluctuations, further supporting structural compactness. The total binding free energy of the hesperetin-MMP9 complex during the 100 ns simulation was (?142.3±6.3) kJ/mol, with minimal energy fluctuations, confirming that the complex remained structurally stable without significant energy transition throughout the simulation.Conclusions:Hesperetin may bind effectively to targets such as MMP9, JAK2, Bcl-2, and ER1, and form a stable complex with MMP9. It is suggested to influence biological processes related to lipids and signaling pathways such as atherosclerosis, diabetic cardiomyopathy, and hypoxia-inducible factor-1, thereby playing a role in heart failure intervention.