OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective To explore the effect of management model of clinical pharmacists participating in multidisciplinary collaborative diagnosis and treatment(MDT)for new anti-tumor drugs in the national medical insurance drug negotiation(hereinafter referred to as"national negotiation"),including efficacy,safe-ty,economy and rationality.Methods The medical records of 326 cases using novel anti-tumor drugs by na-tional negotiation and conforming to the including and excluding standards in this hospital from July 2018 to June 2023 were retrospectively analyzed.The patients were divided into the MDT group(n=122)and non-MDT group(n=204).The patients diagnosed as non-small cell lung cancer(NSCLC)in the two groups were extracted and defined as the MDT-NSCLC subgroup(n=41)and non-MDT-NSCLC subgroup(n=77).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR)and the indexes such as survival quality and medical quality control were compared between the groups.Results The median PFS in the two groups was 12.7 months and 8.0 months,the median OS was 75.2 months and 56.3 months,DCR was 96.72％and 81.86％respectively,and the differences were statistically significant(P＜0.05).The COX multivariate regression analysis indicated that the HR value of clinical pharmacists participating in MDT was higher than the other influencing factors.The median PFS time in the MDT-NSCLC subgroup and non-MDT-NSCLC subgroup was 10.5 months and 6.7 months,DCR was 97.30％and 75.64％respectively,and the differences were statistically significant(P＜0.05),the median OS time was 55.1 months and 40.3 months respectively,and the difference was statistically significant(P＞0.05).The COX multivariate regression anal-ysis indicated that the HR value with clinical pharmacists participating in MDT was higher than the other in-fluencing factors;The adverse reaction occurrence rate in the MDT group and non-MDT group was 45.9％and 58.3％respectively,and the difference was statistically significant(P＜0.05).The KPS score after treatment in the MDT group was higher than that in the non-MDT group,and the difference was statistically significant;in the aspect of medical quality control,the average drug proportion in the MDT group and non-MDT group was 63.93％and 64.54％respectively,the rational drug rate of comments on prescription was 98.36％and 88.73％respectively,the patient satisfaction average value was 90.69 points and 87.36 points respectively and the differences were statistically significant(P＜0.05).Conclusion Clinical pharmacists participating in MDT related to novel anti-tumor drugs by national negotiation is beneficial to improve the therapeutic effects,living quality and patient satisfaction,also benefit to management and control of off-label drug use and medical quality control indexes.

Background and Aims:Implant-based breast reconstruction is one of the most common reconstructive approaches after mastectomy for breast cancer.However,the incidence of postoperative complications remains significant,and the associated risk factors have not been fully elucidated.This study aimed to analyze the incidence of surgical complications following implant-based breast reconstruction in patients undergoing mastectomy at our center and to identify potential risk factors.Methods:A retrospective analysis was conducted on patients who underwent mastectomy and implant-based breast reconstruction at Sun Yat-sen Memorial Hospital between May 2004 and August 2022.Patients were grouped according to the presence or absence of postoperative surgical complications,and multivariate Logistic regression was used to identify independent risk factors.Results:A total of 545 patients with 602 reconstructed breasts were included.Surgical complications occurred in 13.6%(82/602)of the cases,including infection,wound dehiscence/poor healing,flap or nipple-areola necrosis,and implant leakage/rupture.Multivariate analysis revealed that nipple-areola complex resection(OR=1.934,95%CI=1.056-3.542,P=0.033),postoperative radiotherapy(OR=2.483,95%CI=1.527-4.036,P<0.001),implant volume≥300 mL(OR=1.663,95%CI=1.025-2.696,P=0.039),and surgeon experience with fewer than 10 cases(OR=1.804,95%CI=1.092-2.979,P=0.021)were all independent risk factors for complications.Conclusion:NAC resection,radiotherapy,large implant volume,and limited surgical experience are important independent risk factors for postoperative surgical complications following implant-based breast reconstruction.Thorough preoperative evaluation and appropriate surgical planning are essential to minimize risks.

Radiation therapy is a major treatment modality for many malignant tumors. However, patients exhibit marked individual differences in radiosensitivity. Radiation resistance is persistently strengthened through the antioxidant pathway mediated by sulfiredoxin-1 (SRXN1), forming a key bottleneck in improving therapeutic efficacy. Studies have shown that SRXN1 displays dual regulatory roles in the response to radiation. On one hand, SRXN1 enhances cystine uptake and glutathione synthesis via the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2)/solute carrier family 7 member 11 (SLC7A11) axis, thereby suppressing lipid peroxidation-induced ferroptosis and promoting radioresistance. On the other hand, excessive activation of the SRXN1-regulated thioredoxin system depletes reduced nicotinamide adenine dinucleotide phosphate, triggering disulfidptosis through actin cytoskeleton depolymerization. This dynamic equilibrium mechanism reveals for the first time that SRXN1 determines radiosensitivity through time-dependent regulation of two interconnected cell death pathways. This article systematically elucidates how SRXN1 dynamically modulates the radiosensitivity of malignant tumors via the ferroptosis-disulfidptosis interaction network, and reviews the underlying molecular mechanisms, providing a theoretical foundation for developing dual-death-inducing nanomedicines.

Background and Aims:Implant-based breast reconstruction is one of the most common reconstructive approaches after mastectomy for breast cancer.However,the incidence of postoperative complications remains significant,and the associated risk factors have not been fully elucidated.This study aimed to analyze the incidence of surgical complications following implant-based breast reconstruction in patients undergoing mastectomy at our center and to identify potential risk factors.Methods:A retrospective analysis was conducted on patients who underwent mastectomy and implant-based breast reconstruction at Sun Yat-sen Memorial Hospital between May 2004 and August 2022.Patients were grouped according to the presence or absence of postoperative surgical complications,and multivariate Logistic regression was used to identify independent risk factors.Results:A total of 545 patients with 602 reconstructed breasts were included.Surgical complications occurred in 13.6%(82/602)of the cases,including infection,wound dehiscence/poor healing,flap or nipple-areola necrosis,and implant leakage/rupture.Multivariate analysis revealed that nipple-areola complex resection(OR=1.934,95%CI=1.056-3.542,P=0.033),postoperative radiotherapy(OR=2.483,95%CI=1.527-4.036,P<0.001),implant volume≥300 mL(OR=1.663,95%CI=1.025-2.696,P=0.039),and surgeon experience with fewer than 10 cases(OR=1.804,95%CI=1.092-2.979,P=0.021)were all independent risk factors for complications.Conclusion:NAC resection,radiotherapy,large implant volume,and limited surgical experience are important independent risk factors for postoperative surgical complications following implant-based breast reconstruction.Thorough preoperative evaluation and appropriate surgical planning are essential to minimize risks.

Radiation therapy is a major treatment modality for many malignant tumors. However, patients exhibit marked individual differences in radiosensitivity. Radiation resistance is persistently strengthened through the antioxidant pathway mediated by sulfiredoxin-1 (SRXN1), forming a key bottleneck in improving therapeutic efficacy. Studies have shown that SRXN1 displays dual regulatory roles in the response to radiation. On one hand, SRXN1 enhances cystine uptake and glutathione synthesis via the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2)/solute carrier family 7 member 11 (SLC7A11) axis, thereby suppressing lipid peroxidation-induced ferroptosis and promoting radioresistance. On the other hand, excessive activation of the SRXN1-regulated thioredoxin system depletes reduced nicotinamide adenine dinucleotide phosphate, triggering disulfidptosis through actin cytoskeleton depolymerization. This dynamic equilibrium mechanism reveals for the first time that SRXN1 determines radiosensitivity through time-dependent regulation of two interconnected cell death pathways. This article systematically elucidates how SRXN1 dynamically modulates the radiosensitivity of malignant tumors via the ferroptosis-disulfidptosis interaction network, and reviews the underlying molecular mechanisms, providing a theoretical foundation for developing dual-death-inducing nanomedicines.

Interleukin-1 receptor-related kinase (IRAK4) is a widely expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 plays a pivotal role as a key kinase within the downstream signaling pathway cascades of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs). The signaling pathways orchestrated by IRAK4 are integral to inflammatory responses, and its overexpression is implicated in the pathogenesis of inflammatory diseases, autoimmune disorders, and cancer. Consequently, targeting IRAK4-mediated signaling pathways has emerged as a promising therapeutic strategy. Small molecule inhibitors and degraders designed to modulate IRAK4 have shown efficacy in mitigating related diseases. In this paper, we will provide a detailed description of the structure and function of IRAK4, the role of IRAK4 in related diseases, as well as the currently reported small molecule inhibitors and degraders of IRAK4. It is expected to provide new directions for enriching the clinical treatment of inflammation and related diseases.

ObjectiveTo elucidate the underlying mechanism of the efficacy of Levo-tetrahydropalmatine （l-THP） in alleviating chronic pain and identify the key metabolites and metabolic pathways for l-THP regulation. MethodA classical chronic constrictive injury （CCI） model was built in rats’ bodies， and the pain intensity was evaluated by detecting the mechanical withdrawal threshold. On the sixth day after surgery， oral administration of l-THP （64 mg·kg^-1） and positive control drug pregabalin （Pre， 30 mg·kg^-1） was performed on rats. After the last administration following consecutive five times of administration， ipsilateral spinal cord tissues were collected for widely-targeted metabonomics， with eight rats in each group. Differential metabolites （DEMs） were identified according to the standard of VIP>1.0 and P<0.05， and functional enrichment and interaction analyses of the Kyoto Encyclopedia of Genes and Genomes （KEGG） were performed to obtain the key metabolites and metabolic pathways associated with the analgesic effects of l-THP. ResultIn behavioral science， administration of both l-THP and Pre significantly improved mechanical hyperalgesia in CCI rats （P<0.01）， thus mitigating pain. Metabonomic analysis results revealed that l-THP administration corrected the aberrant metabolic profile in the spinal cord of CCI rats. Meanwhile， 53 DEMs were called back， including several classical pain biomarkers such as sphingosine-1-phosphate （S1P）， cyclic adenosine monophosphate （cAMP）， acetylcholine， and glutamate. Functional enrichment analysis of the DEMs indicated the involvement of metabolic pathways such as ferroptosis， autophagy， neuroactive ligand-receptor interactions， phospholipase D and cAMP-related signaling pathways， glutathione metabolism， and cofactor biosynthesis in mediating the effects of l-THP on the metabolic profile of the spinal cord. Further analyses on the relative metabolite abundance and metabolic pathways indicated that by significantly decreasing the relative levels of glutamate （P<0.01） and glycine （P<0.01） in the spinal cord， l-THP can promote the synthesis of reduced glutathione （GSH） and increase the ratio of reduced/oxidized GSH （P<0.05）. Additionally， it can relieve oxidative stress in the spinal cord of CCI rats and significantly reduce the acetyl-CoA level （P<0.01） to finally inhibit ferroptosis occurrence. Conclusionl-THP may exert analgesic effects by regulating multiple metabolic pathways including GSH metabolism， ferroptosis， cofactor biosynthesis， and amino acid synthesis to correct the aberrant metabolic profile in the spinal cord of CCI rats. Ferroptosis and GSH metabolism may be the key pathways for l-THP regulation， with glutamate， glycine， glutathione， and acetyl-CoA as the key metabolites.

OBJECTIVE To analyze the pharmaceutical service process in a fracture patient complicated by fat embolism syndrome （FES） following postoperative fracture， aiming to provide a reference for clinical treatment and pharmaceutical service for similar patients. METHODS Clinical pharmacist participated in the entire treatment process of a patient with FES following postoperative fracture. Based on the patient’s clinical manifestations and test results， literature was reviewed to assist clinical physicians in formulating the therapeutic regimen of glucocorticoids. For the drug-related adverse reactions of renal function impairment and reduced platelet count that occurred during the treatment， suspicious drugs were analyzed and disposed of accordingly. RESULTS The clinical pharmacist recommended Hydrocortisone sodium succinate for injection （100 mg， q8 h， ivgtt， for about one week followed by a gradual dose reduction） for treating FES. The Vancomycin hydrochloride for injection used in this case was assessed as “very probably” associated with the adverse drug reactions of renal function impairment and thrombocytopenia. The clinical physician adopted the pharmacist’s medication recommendations， and the patient’s condition stabilized after treatment， with improvement in adverse reactions， and was discharged from the hospital. CONCLUSIONS The use of glucocorticoids in treating FES has a definite therapeutic efficacy. Clinical pharmacists should individualize the medication plan based on the patient’s pathological state and distinguish it from postoperative sepsis. Meanwhile， drug-induced adverse reactions in the kidney and blood system should be closely monitored.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.