The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

The theory of five spirits(mind,eternal soul,corporeal soul,consciousness and will)is an important part of traditional Chinese medicine(TCM)theory,which reveals the human mental and psychological activities.Five-spirit theory takes the shape of modern cognitive psychology.Language is an important part of cognitive activities.Under the guidance of the five-spirit theory of TCM,and by combining the research results of modern cognitive psychology,this paper initially constructs a language processing model,and proposes that heart-mind,spleen-consciousness,kidney-will,and liver-soul are all involved in the formation of language.Moreover,the pathogenesis of post-stroke aphasia(PSA)is explored from the perspective of the five spirits.It is proposed that PSA refers to the comorbidity of body and spirit,and its pathogenesis is related to the disorders of the five spirits.After analyzing the clinical manifestations of PSA,it is suggested that malnutrition of heart-mind and insufficient kidney-will contribute to the pathogenesis of auditory comprehension and reading obstacles in patients with PSA,and the deactivation of liver-soul is closely related to spontaneous speech and naming obstacles.The treatment of PSA should be focused on nourishing blood and tranquilizing mind,enhancing consciousness and strengthening will,and suppressing liver to tranquilize soul.And the prescriptions of Pingbu Zhenxin Pills,Zhiyi Decoction plus Dingzhi Pills,and Dinghun Decoction can be chosen for modified use.The acupuncture and moxibustion can also be used for PSA,by performance mainly on the acupoints of heart meridians,pericardial meridians,spleen meridians,kidney meridians and liver meridians.The syndrome differentiation and treatment system for PSA with the combination of Chinese medicine and acupuncture based on the five-spirit theory makes up for the shortcomings of stress on the physique while ignorance of the spirit in the conventional zang-fu organ syndrome differentiation,and expands the methods for early intervention of PSA with TCM and approaches to improve the prognosis of rehabilitation.

OBJECTIVE: To reveal the molecular basis of knee osteoarthritis (KOA) with Yang deficiency and blood stasis syndrome by analyzing the gene expression profiles in synovial fluid and blood of KOA patients with this syndrome. METHODS: A total of 80 KOA patients were recruited from October 2022 to June 2024, including 40 cases in the non-Yang deficiency and blood stasis group (27 males and 13 females), with an average age of (61.75±3.45) years old;and 40 cases in the Yang deficiency and blood stasis group (22 males and 18 females), with an average age of (62.00±2.76) years old. The levels of body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), fibrinogen, total cholesterol, and D-dimer were recorded and summarized. Blood and synovial fluid samples from patients were collected for gene expression profile microarray sequencing, and then PCR and immunohistochemistry were used for clinical verification on the patients' synovial fluid and cartilage samples. RESULTS: Logistic regression analysis showed that compared with KOA patients with non-Yang deficiency and blood stasis syndrome, those with Yang deficiency and blood stasis syndrome had increased BMI, LDL, fibrinogen, total cholesterol, and D-dimer, and decreased HDL, with a clear correlation between the two groups. There were 562 differential genes in the blood, among which 322 were up-regulated and 240 were down-regulated;755 differential genes were found in the synovial fluid, with 350 up-regulated and 405 down-regulated. KEGG signaling pathway analysis of synovial fluid revealed changes in lipid metabolism-related pathways, including cholesterol metabolism, fatty acid metabolism, and PPARG signaling pathway. Analysis of the involved differential genes identified 6 genes in synovial fluid that were closely related to lipid metabolism, namely LRP1, LPL, ACOT6, TM6SF2, DGKK, and PPARG. Subsequently, PCR and immunohistochemical verification were performed using synovial fluid and cartilage samples, and the results were consistent with those of microarray sequencing. CONCLUSION This study explores the clinical and genomic correlation between traditional Chinese medicine syndromes and knee osteoarthritis from the perspective of lipid metabolism, and proves that abnormal lipid metabolism is closely related to KOA with Yang deficiency and blood stasis syndrome from both clinical and basic aspects.
Humans ; Male ; Female ; Middle Aged ; Synovial Fluid/metabolism* ; Osteoarthritis, Knee/metabolism* ; Yang Deficiency/complications* ; Aged

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.

Objective To explore predictive value of modified STOP-BANG questionnaire(MSBQ)for hypoxemia during painless gastroscopy.Methods A total of 300 patients were selected as the study subjects who underwent painless gastroscopy in Zhejiang Cancer Hospital from October to December 2021.The MSBQ and STOP-BANG questionnaire(SBQ)were used for assessment before the examination,and patients were divided into high risk group(total score≥3 points)and low risk group(total score<3 points)according to their scores.The incidence of hypoxemia in high risk group and low risk group of the two scales was observed.The predictive value of MSBQ and SBQ for the risk of hypoxemia during painless gastroscopy was evaluated by receiver operating characteristic(ROC)curve.Results The incidence of hypoxemia in high risk group was significantly higher than that in low risk group(P<0.05).The sensitivity of MSBQ and SBQ to predict the occurrence of hypoxemia in painless gastroscopy was 81.01%and 83.54%,the specificity was 78.28%and 66.06%,and the area under the curve was 0.81 and 0.79,respectively.The prediction efficiency of MSBQ was better.Conclusion MSBQ has a high predictive value for the risk of hypoxemia in painless gastroscopy.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.

Objective To investigate the effectiveness of real-time tracking and virtual reality technology(RTVI)used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome.Methods A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022.Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery.There were 28 patients in the RTVI group(12 males and 16 females),with an average age of(46.2±9.3)years old ranging from 28 to 60 years old.There were 32 patients in the simple Tianji surgical robot group,including 15 males and 17 females,aged(48.2±7.8)years old ranging from 32 to 58.The number of registered fluoroscopy,operation time,total number of intraoperative fluoroscopy,intraoperative blood loss,and hospitalization time of the two groups of patients were observed and recorded.All patients received regular follow-up after surgery,and hip X-rays were routinely reviewed to record Garden alignment index,fracture healing time,postoperative complications,and Harris score.Results All 60 patients were followed up.The RTVI group was followed up for 9 to 16 months with an average of(13.0±l.2)months,and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of(12.0±1.3)months.During the follow-up period,the femoral neck fractures of both groups of patients healed well,and no complications such as internal fixation loosening and incision infection occurred.The number of registered fluoroscopy,operation time,and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group(P＜0.01).There was no statistically significant difference in intraoperative blood loss,hospital stay,Garden alignment index,fracture healing time,and hip Harris score between two groups(P＞0.05).Conclusion Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome,it can effectively reduce the operating time,the number of intraoperative X-ray projections,and the risk of intraopera-tive radiation exposure to patients.It also shortened the learning curve of the operator and better reflected the precision and ef-ficiency of the trauma orthopaedic surgery robot.