Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.

Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.

Objective To assess the efficacy and safety of bronchial arterial chemoembolization(BACE)combined with tislelizumab for advanced non-small cell lung cancer(NSCLC).Methods A total of 30 patients in First Affiliated Hospital of Zhengzhou University with stage Ⅲ-Ⅳ NSCLC from December 2021 to August 2022 were enrolled in this study.All the patients received BACE,which was followed by 200 mg tislelizumab once every 3 weeks until the disease progressed,or the patient developed intolerable adverse effects,or the investigator decided to terminate this drug treatment.The primary study endpoint was progression-free survival(PFS),and the secondary study endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),safety,and quality of life(QoL).Results The median follow-up time was 12 months(range of 1.5-12 months),the median PFS was 10.5 months(95％CI:7.8-13.2 months),and the median OS was not available.The 3-month,6-month,and 12-month ORRs were 63.3％(95％CI:43.9％-80.1％),56.7％(95％CI:37.4％-74.5％),and 30.4％(95％CI:13.2％-52.9％)respectively.The 3-month,6-month,and 12-month DCRs were 80％(95％CI:61.4％-92.3％),76.7％(95％CI:57.7％-90.1％),and 47.8％(95％CI:26.8％-69.4％)respectively.The expression ratio of PD-L1 ≥50％(HR=0.29,P=0.039),tumor having a single feeding artery(HR=0.35,P=0.028),and completion of＞10 cycles of tislelizumab therapy(HR=0.42,P=0.064)were the protective factors for PFS.No ≥grade Ⅲ treatment-related adverse events(TRAEs)occurred.The common below grade Ⅱ TRAEs were nausea,fever,and cough.After one cycle of treatment,the patient's QoL,including overall quality of life,physical functioning,and emotional functioning,was significantly improved.Conclusion For the treatment of patients with advanced NSCLC,BACE plus tislelizumab has satisfactory clinical efficacy and safety.

Natural polyphenols are a group of components widely found in traditional Chinese medicines and have been demonstrated to delay or prevent the development of aging and age-related diseases in recent years. As far as we know, the studies of natural polyphenols in aging and aging-related diseases have never been extensively reviewed. In the present paper, we reviewed recent advances of natural polyphenols in aging and common age-related diseases and the current technological methods to improve the bioavailability of natural polyphenols. The results showed that natural polyphenols have the potential to prevent or treat aging and common age-related diseases through multiple mechanisms. Nanotechnology, structural modifications, and matrix processing could provide strong technical support for the development of natural polyphenols to prevent or treat aging and age-related diseases. In conclusion, natural polyphenols have important potential in the prevention and treatment of aging and age-related diseases.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Background::The causal relationship between visceral adipose tissue (VAT) and gout is still unclear. We aimed to examine the potential association between them using observational and Mendelian randomization (MR) analyses.Methods::In the observational analyses, a total of 11,967 participants (aged 39.5 ± 11.5 years) were included from the National Health and Nutrition Examination Survey. Logistic regression models were used to investigate the association between VAT mass and the risk of gout. In two-sample MR analyses, 211 VAT mass-related independent genetic variants (derived from genome-wide association studies in 325,153 UK biobank participants) were used as instrumental variables. The random-effects inverse-variance weighted (IVW) method was used as the primary analysis. Additional sensitivity analyses were also performed to validate our results.Results::Observational analyses found that an increase in VAT mass (per standard deviation) was associated with a higher risk of gout after controlling for confounding factors (odds ratio [OR] = 1.27, 95% confidence intervals [CI] = 1.11–1.45). The two-sample MR analyses demonstrated a causal relationship between increased VAT mass and the risk of gout in primary analyses (OR = 1.78, 95% CI = 1.57–2.03). Sensitivity analyses also showed similar findings, including MR-Egger, weighted median, simple mode, weighted mode, and leave-one-out analyses.Conclusions::Observational analyses showed a robust association of VAT mass with the risk of gout. Meanwhile, MR analyses also provided evidence of a causal relationship between them. In summary, our findings suggested that targeted interventions for VAT mass may be beneficial to prevent gout.

Adenosine has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase(CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells, B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment, making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.

Objective To investigate the expression of tumor protein p53 inducible nuclear protein 2 (TP53INP2) and solute carrier organic anion transporter family member 2A1 (SLCO2A1) in differentiated thyroid carcinoma (DTC) and their relationship with clinicopathological features and prognosis. Methods A total of 80 DTC patients who underwent radical thyroidectomy in the Third Affiliated Hospital of Nanjing Medical University from March to May 2024 were selected. The expression of TP53INP2 and SLCO2A1 in cancer tissue,paracancer tissue and lymph node metastasis tissue of DTC patients were compared,and the relationship between TP53INP2 and SLCO2A1 with clinicopathologic features of DTC patients were analyzed. Expression matrix,clinicopathological parameters and prognostic data of normal thyroid and DTC tissues were downloaded from The Cancer Genome Atlas (TCGA) database,and gene set variation analysis (GSVA) was performed using R software. The relationship between GSVA score and clinicopathological features and prognosis of DTC patients was analyzed. Kaplan-Meier method was used to analyze the relationship between gene set GSVA score and progress free survival (PFS) in DTC patients. Cox univariate and multivariate analysis was used to investigate the factors affecting the prognosis of DTC patients. Results The expressions of TP53INP2 and SLCO2A1 in cancer tissues and lymph node metastasis tissues of DTC patients were significantly decreased (P<0.05). GSVA score was significantly correlated with tumor invasion,lymph node metastasis,distant metastasis and pathological type (P<0.05). The PFS rate of DTC patients with low GSVA score was significantly lower than that of those with high GSVA score (P<0.05). Cox multifactor analysis showed that tumor invasion and low GSVA score were independent factors leading to poor prognosis in DTC patients (P<0.05). Conclusion The expression of TP53INP2 and SLCO2A1 is decreased in DTC tissues,which is associated with tumor invasion,lymph node metastasis,distant metastasis and poor prognosis,and may be a potential target for prognostic judgment in DTC patients.

The pathogenesis of diabetic nephropathy(DN)is very complex.Ferroptosis as a kind of new way of cell death has become a research hotspot in recent years.It is widely known that DN is closely related to ferroptosis.Deactivation of system Xc--GSH-GPX4 axis,iron overload,lipid peroxidation and mitochondrial dysfunction play important role in occurrence and development of ferroptosis of DN,antioxidant protein may be a potential target for the treatment of ferroptosis of DN.Different pathways and interactions may alleviate the occurrence and development of ferroptosis by activating antioxidant protein such as GPX4,Nrf2,Sirtuin family protein and ferritin.Traditional Chinese medicine(TCM)has the characteristics of multi-component,multi-target and multi-pathway overall regulation.The active components and compounds of TCM have potential application value in improving renal injury and ferroptosis of DN by enhancing the expression of antioxidant protein,which provides a new research direction for delaying the progress of DN.

Objective To observe the effect of non-invasive ventilator assisted vibration sputum evacuation on the level of cardiac function indicators in patients with acute heart failure in the intensive care unit(ICU).Methods A total of 120 patients with acute heart failure who received treatment in the ICU of Tongde Hospital of Zhejiang Province from September 2020 to March 2023 were selected as the study subjects.The patients were randomly divided into a control group and an experimental group using a random number table method,with 60 patients in each group.A total of 120 patients were treated with conventional symptom therapy and non-invasive ventilation.The control group received routine nursing intervention,while the experimental group received non-invasive ventilator assisted vibration sputum evacuation.Arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),pulse oxygen saturation(SpO2),respiratory rate(RR),heart rate,blood pressure,central venous pressure,serum and ultrasound cardiac function indicators,and prognosis of two groups of patients were recorded after 2 weeks of intervention.Results After the intervention,PaO2,SpO2,and left ventricular ejection fraction(LVEF)were significantly increased in both groups,while PaCO2,RR,heart rate,blood pressure,central venous pressure,N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin T(cTnT),left ventricular end-systolic diameter(LVESD),and left ventricular end-diastolic diameter(LVEDD)were significantly decreased compared to before the intervention(all P<0.05).Compared with the control group,the experimental group showed significant increases in PaO2,SpO2,blood pressure,central venous pressure,and LVEF after intervention[PaO2(mmHg,1 mmHg≈0.133 kPa):68.24±5.81 vs.59.63±6.86,SpO2:0.95±0.03 vs.0.87±0.04,systolic blood pressure(mmHg):116.05±4.11 vs.104.13±3.95,diastolic blood pressure(mmHg):68.19±4.13 vs.62.85±4.12,central venous pressure(mmHg):9.42±1.29 vs.8.12±4.12,LVEF:0.49±0.05 vs.0.43±0.04,all P<0.05],while PaCO2,RR,heart rate,NT-proBNP,cTnT,LVESD,and LVEDD were significantly reduced[PaCO2(mmHg):42.12±4.08 vs.52.13±4.61,RR(beats/min):18.85±1.75 vs.21.54±2.51,heart rate(bpm):89.53±8.14 vs.101.11±10.26,NT-proBNP(ng/L):1687.25±589.67 vs.2145.36±751.03,cTnT(ng/L):70.58±5.15 vs.81.45±6.89,LVESD(mm):34.51±3.11 vs.38.89±3.55,LVEDD(mm)46.11±3.22 vs.49.74±3.75,all P<0.05].The mechanical ventilation time,ICU hospitalization time,and pulmonary infection relief time of the experimental group were significantly shortened compared to the control group[mechanical ventilation time(hours):72.14±10.06 vs.78.96±12.97,ICU hospitalization time(days):10.74±2.15 vs.12.88±3.26,pulmonary infection relief time(days):3.58±0.79 vs.5.14±1.12,all P<0.05],and the incidence of pulmonary infection was significantly reduced[1.67%(1/60)vs.11.67%(7/60),P<0.05],However,there was no statistically significant difference in the mortality rate between the experimental group and the control group[10.00%(6/60)vs.21.67%(13/60),P>0.05].Conclusion The non-invasive ventilator assisted vibration sputum evacuation can improve symptoms of hypoxemia and cardiac function,stabilize hemodynamics,shorten the course of acute heart failure in ICU patients,and reduce the incidence of pulmonary infections.