AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Objective: To summarize the long-term efficacy and safety of sacral neuromodulation (SNM) in treating refractory interstitial cystitis/bladder pain syndrome (IC/BPS)，so as to provide clinical evidence for this therapeutic approach. Methods: This study retrospectively analyzed the data of 27 patients with refractory IC/BPS treated at our hospital during Jan.2015 and Dec.2021.All patients underwent SNM Ⅱ.The therapeutic effects were evaluated with Global Response Assessment (GRA).The preoperative and postoperative daily urinary frequency，nocturia frequency，functional bladder capacity，O'Leary-Sant score，pelvic pain，urgency and frequency (PUF) score，quality of life (QoL) score，and visual analogue scale (VAS) score were compared. Results: During the follow-up of (55.55±16.33) months，12 patients showed no symptom relief (GRA≤4)，while 15 experienced symptom relief (GRA>4)，resulting in an efficacy rate of 55.56% (15/27).The average daily urination frequency decreased from (28.74±13.84) to (24.74±16.33) times,the O'Leary-Sant score decreased from (30.19±5.35) to (25.63±9.34)，PUF score decreased from (25.63±5.34) to (22.04±8.29)，QoL score decreased from (5.67±0.55) to (4.33±1.57)，and VAS score decreased from (8.04±1.91) to (5.33±3.09)，the differences were statistically significant (P<0.05). No complications such as incision infections or pain at the implant site were observed. Conclusion: SNM is safe and effective for refractory IC/BPS，but there is a risk of long-term failure.Therefore，patients should be discreetly selected.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

As a chronic and complex disease,obesity can cause many other diseases.Obesity is influenced by many factors.At present,the main treatment methods for obesity are behavioral intervention,medication,endoscopic therapy,and sleeve gastrectomy.New break-throughs and progress have achieved in medication.This article mainly introduces the latest clinical situation and adverse reactions of several representative drugs in glucagon-like peptide-1 receptor agonists,such as liraglutide,semaglutide,and tirzepatide.This article mainly aims to analyze the safety and efficacy of these anti-obesity drugs and provide guidance for future clinical medication.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective To comparatively evaluate the diagnostic value of metagenomic next-generation sequencing(mNGS)versus conventional microbial culture in spinal infections.Methods A cross-section design was conducted on 82 consecutive patients with suspected spinal infections treated between February 2022 and January 2024 at Jiangbei Branch of First Affiliated Hospital of Army Medical University(Third Military Medical University).Microbiological culture,histopathological examination,and mNGS results from infected specimens were analyzed.Clinical diagnosis,primarily based on clinical manifestations,laboratory tests and radiologic features combined with medical history,was defined as the gold standard,and then the diagnostic performance,including sensitivity and specificity,were compared between mNGS and microbial culture.Results Among the 82 patients,definitive microbiological evidence was identified in 70 cases,and mNGS demonstrated a significantly higher detection rate than microbial culture(64 vs 36 cases,78.05％vs 43.9％,P<0.05).mNGS also obtained obviously higher sensitivity,accuracy,and negative predictive value(NPV),and notably lower positive predictive value(PPV)when compared to conventional microbial culture(all P<0.05).When stratified by infection type,mNGS obtained significantly higher sensitivity and accuracy compared to microbial culture in tuberculous spinal infections(P<0.05).For non-tuberculous spinal infections,mNGS also showed superior sensitivity to microbial culture(P<0.05).Conclusion In patients with spinal infections,mNGS demonstrates a significantly higher pathogen detection rate than conventional microbial culture.This technique can provide early and broad-spectrum pathogenic microbiological evidence for spinal infection.

The gut microbiota plays a crucial role in regulating energy metabolism and obesity progression through mechanisms involving short-chain fatty acid and bile acid metabolism pathways. Obese individuals often exhibit gut microbiota dysbiosis, which can influence lipid metabolism and insulin sensitivity through microbial metabolites and signaling mechanisms. Dietary, pharmaceutical, and bariatric metabolism surgery can modulate the gut microbial, strongly correlating with weight reduction and metabolic benefits. Emerging microbiome-modulating strategies, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can restore microbial homeostasis and improve bile acid processing, but results differ among people. Moreover, the structural specificity of dietary fibers enables targeted microbial modulation, which provide new perspectives for developing anti-obesity therapies. This review summarizes the mechanisms of interaction between gut microbiota and the host and the clinical research progress in obesity intervention.

Objective To explore the application value of predictive model based on nutritional status combined with clinical data in infectious complications after radical gastrectomy for gastric canc-er.Methods The clinical data on 394 gastric cancer patients who underwent radical gastrectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2017 to July 2024 were retrospec-tively collected.According to whether the patients developed infection after surgery,they were divided into infection group(n=73)and non-infection group(n=321)based on whether they developed postoperative infections or not.The least absolute shrinkage and selection operator(LASSO)method was used to obtain the optimal related features associated with infectious complications after radical gas-trectomy for gastric cancer.Multivariate Logistic regression analysis was conducted to screen for risk factors of infectious complications after radical gastrectomy.R software was used to randomly select 70％of data as training set(for establishing the nomogram model)and 30％of data as test set.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve,Bootstrap sampling validation,and decision curve analysis(DCA)were used to assess the value of the predictive model.Results of the 394 gastric cancer patients,73 developed postoperative infectious complications,in-cluding 53.42％with lung infections,17.81％with intra-abdominal infections,16.44％with uri-nary tract infections,and 12.33％with wound infections.Age,diabetes mellitus,preoperative nu-tritional risk,high preoperative PIV,combined organ resection,and prolonged operation time were identified as risk factors for infectious complications after radical gastrectomy(P＜0.05).In the training set,the AUC of the nomogram model was 0.898,and the AUC validated in the test set was 0.891.Bootstrap sampling validation with 1,000 iterations showed that the average errors between the predicted probabilities and actual values in the training and test sets were 0.019 and 0.024,re-spectively.DCA results indicated that the model had clinical utility.Conclusion Infectious com-plications after gastrectomy for gastric cancer are common,and the predictive model based on nutri-tional assessment combined with clinical data has high value in predicting the risk of infectious com-plications after gastrectomy.