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.

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.

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.

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 investigate the biological function of long non-coding RNA(LncRNA)LINC01137 in immune escape of non-small cell lung cancer(NSCLC)cells and its potential regulatory mechanisms.Methods The blood samples of 24 healthy volunteers and 24 NSCLC patients were collected.The tumor tissues and paracancerous tissues of 24 NSCLC patients were collected,and the levels of LINC01137 were detected.The binding sites of LINC01137 and miR-22-3p were predicted by Starbase database and verified by the luciferase reporter gene analysis.A549 cells were transfected with exosomes derived from A549 cells and/or sh-LINC01137 interference sequence to detect cell proliferation and invasion.The supernatant of A549 cells were collected to culture CD8+T cells,and the levels of CD8+T cell exhaustion markers,including interfereron-γ(IFN-γ),tumor necrosis factor-α(TNF-α),granzyme B and interleukin-2(IL-2),and the percentage of PD-1+Tim3+CD8+T cells were detected.CD8+T cells were transfected with exosomes and/or miR-22-3p mimics to detect the protein level of PD-1.Results The expression of LINC01137 in tumor tissues of patients with NSCLC was increased compared with paracancerous tissues(3.357±0.548 vs 1.011±0.371),while the expression of LINC01137 in peripheral blood of patients with NSCLC was increased compared with healthy volunteers(3.216±0.342 vs 1.007±0.313),with statistically significant differences(t=-17.367,-17.147,all P<0.001).There was a positive correlation between the expression of LINC01137 in tumor tissue and peripheral blood(r=0.755,P<0.05).LINC01137 was significantly enriched in exosomes derived from A549 cells.Compared with Exo+sh-NC group,the cell viability(65.85%±4.71%vs 100.15%±11.93%)and cell invasion(21.46%±3.48%vs 43.12%±1.44%)in Exo+sh-LINC01137 group were decreased,and the differences were statistically significant(t=4.630,9.953,all P<0.01).The expression of LINC01137 in peripheral blood of NSCLC patients was negatively correlated with the percentage of CD8+T cells(r=-0.520,P<0.05).Compared with Exo+sh-NC group,the IFN-γ(3 865.31±543.85 pg/ml vs 1 786±105.98 pg/ml),TNF-α(4 631.93±510.71 pg/ml vs 1 973.24±379.62 pg/ml),Granzyme B(3 876.49±312.43 pg/ml vs 1 879.43±287.58 pg/ml),and IL-2 mRNA levels(3.286±0.437 vs 1.015±0.314)were increased,and the percentage of PD-1+Tim3+CD8+T cells(7.68%±2.18%vs 18.95%±3.21%)was decreased in Exo+sh-LINC01137 group,with statistical significances(t=-6.497,-7.237,-8.146,-7.310,5.021,all P<0.01).Our results showed that miR-22-3p was the target gene of LINC01137.Compared with Exo+NC mimic group,the level of PD-1 protein in Exo+miR-22-3p group(0.384±0.087 vs 1.003±0.147)was significantly decreased,and the difference was statistically significant(t=6.277,P<0.01).Conclusion The expression of LINC01137 was significantly up-regulated in tumor tissues and plasma of NSCLC patients.Exosomes LINC01137 derived NSCLC cell induces CD8+T cell exhaustion by targeting miR-22-3p and inhibiting its expression,and thus promoting NSCLC cell immune escape.

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.

Objective:To compare the effects of drug-loaded microsphere TACE (D-TACE) and iodinated oil emulsion TACE (cTACE) on liver fibrosis in the treatment of advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 113 patients with HCC treated with D-TACE or cTACE at the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed, including 96 males and 17 females, aged (56.8±9.8) years old. According to treatment protocol, patients were divided into two groups: the D-TACE group ( n=57) and the cTACE group ( n=56). Liver fibrosis panel, fibrosis index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared between the groups at four timepoints: pre-treatment, one month after the first TACE, one month after the second TACE, and 12 months after the first TACE. Follow-ups were conducted through outpatient visits or telephone reviews to assess patient survivals. Data including the progression-free survival (PFS) and number of TACE sessions were compared between the two groups. Results:The D-TACE group received 2.84±1.12 sessions of treatment during the observation period, compared to 4.05±1.44 sessions of cTACE group ( t=4.94, P<0.001). The median PFS in D-TACE and cTACE groups were 10.0 and 5.0 months, respectively ( P<0.001). At one month after the second TACE and at 12 months after the first TACE, patients in cTACE group had a higher serum levels of fibrosis markers including hyaluronic acid, type IV collagen, type III procollagen N peptide and laminin than those in D-TACE group (all P<0.05). At the same timepoints, patients in cTACE group also had higher APRI, FIB-4 and LSM than those in D-TACE group (all P<0.05). Conclusion:Compared to cTACE, patients in D-TACE group received fewer sessions of treatment during the first year after initial TACE, and the degree of liver fibrosis was also lower in D-TACE group.

Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization (DTACE) combined with apatinib for unresectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) after the application of camrelizumab, and the secondary endpoints were objective remission rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). The Kaplan-Meier method was used to plot survival curves, the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics, and the influencing factors for prognosis were analyzed. Results A total of 89 patients were screened and followed up in this study. The patients were followed up to December 2021, with a median follow-up time of 16 months, a median OS time of 17.0 (95% confidence interval [ CI ]: 15.3-18.7) months, and a median PFS time of 7.0 (95% CI : 6.2-7.8) months. There were significant differences in OS and PFS between the patients with different ECOG-PS scores, liver function Child-Pugh classes, portal vein invasion, patterns of progression, times of DTACE treatment, durations of oral administration of apatinib, and durations of application of camrelizumab (all P < 0.05). At 3 and 6 months after the application of camrelizumab, ORR was 39.3% and 22.4%, respectively, and DCR was 80.9% and 54.1%, respectively. The univariate analysis using the Log-rank test showed that compared with the patients receiving 0 time of DTACE treatment, the patients receiving 3-4 or 1-2 times of DTACE treatment had significant improvements in median OS [22.0 (95% CI : 21.1-22.9) months and 17.0 (95% CI : 15.8-18.2) months vs 10.0 (95% CI : 7.0-13.0) months, χ 2 =31.423, P < 0.001] and PFS [10.0 (95% CI : 7.0-13.0) months and 7.0 (95% CI : 6.2-7.8) months vs 3.0 (95% CI : 1.9-4.1) months, χ 2 =20.741, P < 0.001]; compared with the patients using apatinib for ≤4 months, the patients using apatinib for > 4 months had significant improvements in median OS [21.0 (95% CI : 19.1-22.9) months vs 14.0 (95% CI : 10.4-17.6) months, χ 2 =19.399, P < 0.001] and PFS [9.0 (95% CI : 7.3-10.7) months vs 5.0 (95% CI : 4.0-6.0) months, χ 2 =27.733, P < 0.001]; compared with the patients using camrelizumab for ≤5 months, the patients using camrelizumab for > 5 months had significant improvements in median OS [22.0 (95% CI : 20.2-23.8) months vs 13.0 (95% CI : 9.3-16.7) months, χ 2 =22.336, P < 0.001] and PFS [9.0 (95% CI : 7.0-11.0) months vs 5.0 (95% CI : 4.1-5.9) months, χ 2 =26.141, P < 0.001]. Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment. Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment, with no grade ≥4 adverse reactions, and no patients withdrew from target-free therapy due to TRAEs. Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC, camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.

Objective:To observe the short-term efficacy and safety of bronchial arterial chemoembolization (BACE) combined with anlotinib for treatment of advanced non-small cell lung cancer (NSCLC).Methods:The clinical data of 14 patients with advanced NSCLC in the First Affiliated Hospital of Zhengzhou University from June 2018 to March 2019 were retrospectively analyzed. The short-term efficacy and adverse reactions of BACE combined with anlotinib hydrochloride were evaluated.Results:All patients successfully received BACE treatment twice. The median follow-up time was 19 months (8-26 months). The objective response rate (ORR) of patients at 1, 3 and 6 months after the first treatment was 100.0% (14/14), 71.4% (10/14) and 57.1% (8/14), and the disease control rate (DCR) was 100.0% (14/14), 92.8% (13/14) and 78.6% (11/14), respectively. The median progression-free survival (PFS) time was 9.5 months (95% CI 9.0-17.3 months), and the 6-month and 12-month PFS rates were 78.6% and 28.6%, respectively. The median overall survival (OS) time was 19.0 months (95% CI 18.4-23.1 months), and the 6-month and 12-month OS rates were 100.0% and 85.7%, respectively. Anlotinib hydrochloride-related adverse reactions included hand-foot syndrome [42.9% (6/14)], fatigue [35.7% (5/14)], hypertension [35.7% (5/14)], oral mucositis [28.6% (4/14)], hemoptysis [28.6% (4/14)], elevated aminotransferases [21.4% (3/14)] and diarrhea [14.3% (2/14)]. There were no grade ≥3 adverse reactions. Conclusion:BACE combined with anlotinib is safe and effective for treatment of advanced NSCLC, and the short-term clinical efficacy is satisfactory.

Objective:To investigate the effect of adjuvant radiotherapy on the prognosis of patients with N 2 stage non-small cell lung cancer (NSCLC) undergoing radical resection. Methods:The data of 1 208 patients with NSCLC who received radical lung cancer resection combined with chemotherapy or post-operative adjuvant radiotherapy and chemotherapy from SEER database of the United States from 2004 to 2016 were included in the study. 627 patients received radical lung cancer resection combined with chemotherapy (surgery + chemotherapy group), and 581 patients received radical lung cancer resection combined with radiochemotherapy (surgery + radiochemotherapy group). We analyzed and compared the effect of postoperative adjuvant radiotherapy on the prognosis of patients with N 2 stage NSCLC undergoing radical resection. The 1∶1 propensity matching method was used to analyze the prognosis of the two groups. Results:In the two groups of patients with stage N 2 NSCLC included in the study, the median survival time was 51 months in the operation + radiotherapy and chemotherapy group, and the 3- and 5-year cancer specific survival rates were 58.3% and 44.9%, respectively. The median survival time was 50 months in operation + chemotherapy group, and the 3- and 5-year cancer specific survival rates were 59.9% and 46.5%, respectively. There was no statistically significant difference between the two groups in cancer specific survival ( P>0.05). The result of subgroup analysis showed that the cancer specific survival of patients in operation + radiotherapy and chemotherapy group was significantly worse than that in operation + chemotherapy group ( χ2=5.085, P<0.05). Multivariate Cox regression analysis showed that age, gender, G stage, T stage and the number of lymph node metastasis were the important factors affecting the cancer specific survival of patients with N 2 NSCLC ( Wald =15.236, 7.039, 4.841, 10.155, 11.192, respectively, P<0.05). After propensity matching, there was no statistically significant difference in cancer specific survival ( P>0.05) between the two groups. However, in the T 1 NSCLC patients, the cancer specific survival of operation + radiochemotherapy group was significantly worse than that of operation + chemotherapy group ( χ2=5.364, P<0.05), while the cancer specific survival of operation + radiochemotherapy group was significantly better than that of operation + chemotherapy group in T 3-4 subgroup( χ2=4.486, P<0.05). According to the tendency matching of pathological subgroups, the cancer specific survival of surgery + radiochemotherapy group was significantly better than that of surgery + chemotherapy group ( χ2=6.279, P<0.05) in the non adenocarcinoma subgroup. And the multivariate Cox regression analysis indicated that postoperative radiotherapy was an important factor for cancer specific survival in patients with N 2 non adenocarcinoma non-small cell lung cancer ( Wald=7.300, P<0.05). However, before and after propensity matching in lung adenocarcinoma subgroup, there was no statistically significant difference in cancer specific survival between the surgery + radiochemotherapy group and the surgery + chemotherapy group ( P>0.05). Conclusions:Postoperative adjuvant radiotherapy can improve the prognosis of patients with T 3-4 or non-adenocarcinoma N 2 NSCLC. But, for other patients with N 2 non-small cell lung cancer, the choice of postoperative adjuvant radiotherapy should be cautious, especially for T 1 stage.