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 clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

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 study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

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 study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

Diabetic peripheral neuropathy (DPN) is one of the chronic complications of diabetic neuropathy, and also the main cause of chronic wounds and disability. Exosomes and exosomal-microRNAs (miRNAs) are closely related to DPN and participate in the signal transduction and protein expression of the peripheral nervous system by mediating intercellular communication. However, the specific role and mechanism of EVs and exosomal-miRNAs in the occurrence and development of DPN in high-glucose environments are not fully understood. This article reviews the promotion of EVs and exosomal-miRNAs in the occurrence and development of DPN in inhibiting axon growth, promoting inflammatory response, and inducing vascular injury in a high glucose environment.

Objective To explore the differential microbiota in patients with newly diagnosed type 2 diabetes mellitus(T2DM),and to preliminarily evaluate the importance of the differential core microbiota in the metabolic disorder.Methods A total of 30 T2DM patients who were treated at the Endocrinology Department of our hospital from September to November 2020,and 30 healthy individuals taking physical examination during the same period were enrolled and assigned into the T2DM group and the control group,respectively.Their blood and fecal samples were collected for the detection of glucose,insulin,and lipid indicators levels and for gut microbiota using 16SrRNA,respectively.Subsequently,bioinformatics analysis,Pearson correlation analysis,and other statistical methods were applied to analyze the differences in T2DM blood indicators and specific bacterial species between the 2 groups.RT-qPCR was used to verify the screening results of small RNA profiles.Then a multi-parameter receiver operating characteristic(ROC)curve model was constructed based on the results of correlation analysis including microbiome,lipid metabolome and miRNAs spectrum genomic detection data of early research.Results T2DM showed specific characteristics of intestinal microbiota,with Phascolarctobacterium and Phascolarctobacterium.faecium(P.faecium)showing significant differences before and after the onset of the disease.Pearson correlation analysis suggested that P.faecium was negatively correlated with high-density lipoprotein(HDL)(r=-0.78,P＜0.001),low-density lipoprotein(LDL)(r=-0.89,P＜0.001),and insulin(r=-0.71,P＜0.001).While,Phascolarctobacterium was negatively correlated with insulin(r=-0.67,P＜0.001)and body mass index(BMI)(r=-0.64,P＜0.001).The ROC curve model based on Phascolarctobacterium/P.faecium,α-linolenic acid,and miR-122-5p could accurately distinguish between T2DM patients and healthy individuals,with a value of area under the curve of 0.928(P=0.0001)and 0.934(P＜0.0001),which suggesting core values of 2 types of bacteria in the disease.Conclusion T2DM patients have specific gut microbiota distribution,in which Phascolarctobacterium and P.faecium are closely associated with metabolic disorders of the disease.The 2 types of bacteria can be regarded as core bacteria for T2DM.

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.