To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

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 investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital, Fudan University. According to the treatment plan, patients were divided into the conventional treatment group and the Huangkui combination treatment group (Huangkui capsules combined with conventional treatment), and the clinical efficacy between the two groups was compared. The logistic regression analysis was used to identify the main factors affecting treatment efficacy. Results The Huangkui combination treatment group (n＝29) showed a significantly higher overall effective rate (79.3% vs 42.3%, P＝0.005), and an earlier proteinuria improvement (median time: 3 months vs 6 months, P＝0.008) than the conventional treatment group (n＝26) . The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB) using (OR＝0.190, 95%CI 0.045-0.808, P＝0.025), targeted drug adjustment (OR＝0.132, 95%CI 0.030-0.581, P＝0.007), and Huangkui capsules using (OR＝0.168, 95%CI 0.039-0.730, P＝0.017) were protective factors for treatment efficacy of targeted drug-related proteinuria. Conclusions On the basis of conventional treatment, additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

ObjectiveTo explore the effects of vascular endothelial growth factor A （VEGFA） rs2010963 and rs3025039 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors. MethodsA total of 104 pediatric patients with brain tumors receiving standardized chemotherapy were enrolled. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for VEGFA rs2010963 and rs3025039 genotyping. The χ² test was applied to analyze the association between genotypes and chemotherapy‑related toxicities. Cox regression was used to evaluate the correlations of clinicopathological characteristics and genotypes with the progression‑free survival （PFS）. In addition， bioinformatic analyses were conducted to investigate the regulatory factors potentially affected by the two SNP loci. ResultsThe VEGFA expression in brain tumors （5.17±1.81） was significantly higher than that in normal tissues （4.33±1.56， P<0.001）. Patients with high VEGFA expression had significantly worse overall survival than patients with low VEGFA expression （P<0.001）. Among the 104 children with brain tumors included， the rs2010963 CC， CG， and GG genotypes accounted for 14.42%， 55.77%， and 29.81%， respectively. The frequencies of C and G alleles were 42.31% and 57.69%， respectively. The rs3025039 CC， CT， and TT genotypes accounted for 70.19%， 25.96%， and 3.85%， respectively. The frequencies of C and T alleles were 83.17% and 16.83%， respectively. The children with the rs3025039 CC genotype had significantly higher incidences of thrombocytopenia （46.58%） and gastrointestinal toxicity （56.16%） than CT genotype carriers （22.22% and 33.33%， respectively， P<0.05）， and significantly lower incidences of coagulation disorders （4.11%） than TT genotype carriers （50.00%， P<0.05）.The incidence of hyperlipidemia （2.74%） was significantly lower than that in the CT genotype carriers （14.82%， P<0.05）. The tumor type and the rs2010963 genotype were significantly associated with PFS （P<0.05） in univariable and multivariable Cox regression analysis. Bioinformatic analysis indicated that the rs2010963 and rs3025039 polymorphisms regulated VEGFA expression by affecting the binding of transcription factors and miRNAs to their target gene sequences， respectively. ConclusionThe VEGFA rs3025039 CC genotype is a risk factor for thrombocytopenia and gastrointestinal toxicity， and a protective factor for coagulation disorders and hyperlipidemia. The rs2010963 CG genotype is a protective factor for brain tumor progression.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective:To investigate the effect of applying the analog of miR-145(agomiR-145)to target a disintegrin and metallopro-tease 17(ADAM17)on the growth of triple-negative breast cancer(TNBC)xenograft tumors in nude mice and the underlying mecha-nism.Methods:A subcutaneous xenograft tumor model was established in nude mice with MDA-MB-231 cells(n=30).The 30 nude mice were randomly divided into agomiR group,agomiR-NC group,and control group to receive intratumoral injection of 100 μL of agomiR-145(0.33 g/L),agomiR-NC(0.33 g/L),and normal saline,respectively.We examined tumor tissue morphology with HE stain-ing;measured the expression of miR-145,ADAM17,and epidermal growth factor receptor(EGFR)in tumor tissues by real-time poly-merase chain reaction(RT-PCR);and determined the protein expression of ADAM17,EGFR,and p-EGFR in tumor tissues by immu-nohistochemistry and Western blot.Results:The tumor growth in the agomiR group was slow,with a significantly smaller tumor volume than those in the control group and the agomiR-NC group(P<0.05).The results of HE staining showed more severe necrosis and hem-orrhage within tumor tissues in the control group and the agomiR-NC group than in the agomiR group.RT-PCR results showed that the expression level of miR-145 in the agomiR group was significantly higher than those in the agomiR-NC and control groups(P<0.001);the agomiR group had a significantly lower mRNA expression level of ADAM17 than the other two groups(P<0.05);and there was no significant difference in EGFR mRNA expression between the three groups(P>0.05).Immunohistochemistry and Western blot detected significantly lower protein expression levels of ADAM17 and EGFR in the agomiR group than in the agomiR-NC group and the control group(P<0.05).Conclusion:AgomiR-145 inhibits the growth of TNBC xenografts in nude mice by targeted suppression of ADAM17-EGFR activity.

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.