Efficacy and safety analysis of TACE + PEI + lenvatinib compared with TACE + lenvatinib for the treatment of hepatocellular carcinoma with PVTT: a retrospective study.

Objective: The aim of this study was to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) and lenvatinib in HCC patients with PVTT (Vp2-3), thus providing a safe and effective treatment strategy for advanced HCC patients. Materials and methods: Clinical data of 227 patients with unresectable HCC and PVTT treated at the Union Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their treatment methods: TACE+PEI+lenvatinib group (N=103) and TACE+lenvatinib group (N=124). Results: The proportion of patients with disappearance, shrinkage, or no change of PVTT after treatment was significantly higher in the TACE+PEI+lenvatinib group compared to the TACE+lenvatinib group, with statistical significance (P<0.001). The TACE+PEI+lenvatinib group had higher objective response rate (ORR) (50.5% vs. 25.8%, P<0.001) and disease control rate (DCR) (87.4% vs. 74.2%, P=0.013) than the TACE+lenvatinib group. The median progression-free survival (mPFS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (8.1 months vs. 6.5 months, P<0.001). Consistently, the median overall survival (mOS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (17.1 months vs. 13.9 months, P<0.001). Conclusion: Among HCC patients with PVTT (Vp2-3), TACE+PEI+lenvatinib is more effective comparing to TACE+lenvatinib in prolonging PFS and OS. The control of PVTT in the TACE+PEI+lenvatinib group was significantly more satisfactory than that in the TACE+lenvatinib group. TACE+PEI+lenvatinib is a safe and effective treatment strategy for HCC patients with PVTT (Vp2-3).

Analysis of the Efficacy and Safety of Palonosetron Hydrochloride in Preventing Nausea And Vomiting After TACE: A Retrospective Analysis.

PURPOSE: To investigate the mechanism of nausea and vomiting after TACE, and analyze the efficacy and safety of palonosetron hydrochloride in the prevention of nausea and vomiting after TACE. METHODS: The data of 221 patients who underwent TACE in the Department of Intervention Therapy from August 2018 to August 2020 were collected. The patients were divided into two groups: those who did not use palonosetron hydrochloride before TACE (TACE group, N=116); and those who used palonosetron hydrochloride before TACE (TACE+palonosetron group, N=105). Primary study endpoint: The control rate of nausea and vomiting in the two groups at 0-24 h (acute), 24-120 h (delayed), and 0-120 h. Secondary Study Endpoints: Adverse events of palonosetron hydrochloride. RESULTS: TACE group vs TACE+palonosetron group: 0-24h, 74 vs 44 patients with nausea (63.8% vs 41.9%); 24-120 h, 50 vs 16 patients with nausea (43.1% vs 15.2%); 0-120 h after TACE, 81 vs 50 patients with nausea (69.8% vs 47.6%). 0-24h, 52 vs 26 patients with vomiting (44.8% vs 24.8%); 24-120 h, 24 vs 8 patients with vomiting (20.7% vs 7.6%); 0-120 h after TACE, 64 vs 26 patients with vomiting (55.2% vs 24.8%). The incidence of nausea and vomiting after TACE was significantly lower in the TACE+palonosetron group than in the TACE group (p < 0.05). CONCLUSION: Palonosetron hydrochloride can significantly reduce the incidence of nausea and vomiting in patients after TACE, with exact effect and high safety.

Efficacy and safety of tyrosine kinase inhibitors plus PD-1 inhibitor in patients with transarterial chemoembolization- refractory hepatocellular carcinoma: a two-center retrospective study.

Object: To investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC). Materials and methods: Data of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE+TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses. Results: Compared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference. Conclusion: The treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC.

Efficacy and safety analysis of TACE + Donafenib + Toripalimab versus TACE + Sorafenib in the treatment of unresectable hepatocellular carcinoma: a retrospective study.

OBJECTIVE: To compare the efficacy and safety of TACE combined with Donafenib and Toripalimab versus TACE combined with Sorafenib in the treatment of unresectable hepatocellular carcinoma (HCC), aiming to guide personalized treatment strategies for HCC and improve patient prognosis. MATERIALS AND METHODS: A retrospective analysis was conducted on the clinical data of 169 patients with unresectable advanced-stage HCC who underwent treatment at the Interventional Department of Wuhan Union Hospital from January 2020 to December 2022. Based on the patients' treatment strategies, they were divided into two groups: TACE + Donafenib + Toripalimab group (N = 81) and TACE + Sorafenib group (N = 88). The primary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups' tumors. The secondary endpoint was the occurrence of treatment-related adverse events in the two groups of patients. RESULTS: The TACE + Donafenib + Toripalimab group showed higher ORR and DCR compared to the TACE + Sorafenib group (66.7% vs. 38.6%, 82.6% vs. 68.2%, P < 0.05). The TACE + Donafenib + Toripalimab group also demonstrated longer median progression-free survival (mPFS) (10.9 months vs. 7.0 months, P < 0.001) and median overall survival (mOS) (19.6 months vs. 10.9 months, P < 0.001) compared to the TACE + Sorafenib group. When comparing the two groups, the TACE + Sorafenib group had a higher incidence of grade 3-4 hypertension (14.8% vs. 4.9%, P = 0.041), higher incidence of diarrhea (all grades) (18.2% vs. 7.4%, P = 0.042), and higher incidence of hand-foot syndrome (all grades) (26.1% vs. 12.3%, P = 0.032). CONCLUSION: TACE combined with Donafenib and Toripalimab demonstrates superior efficacy and safety in treating unresectable HCC patients. This combination therapy may serve as a feasible option to improve the prognosis of unresectable HCC patients.

Efficacy and safety analysis of dexamethasone + palonosetron in prevention of post-embolization syndrome after D-TACE: A retrospective study.

To investigate the efficacy and safety of dexamethasone + palonosetron in the prevention of post-embolization syndrome after drug-eluting beads transcatheter arterial chemoembolization (D-TACE). The data of 278 patients who received D-TACE from January 2018 to December 2021 were collected and divided into 2 groups: D-TACE group (N = 145) and D-TACE + dexamethasone + palonosetron group (N = 133). The incidence of post-embolization syndrome and infection after D-TACE was assessed in both groups. Incidence of abdominal pain: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 56.6% versus 40.6%, P = .008; incidence of fever: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 40.0% versus 14.3%, P = .000; incidence of nausea: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 61.4% versus 39.8%, P = .001; incidence of vomiting: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 48.3% versus 21.1%, P = .000; incidence of infection: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 1.4% versus 1.5%, P = .931. The combined use of dexamethasone and palonosetron before D-TACE can effectively reduce the incidence of post-embolization syndrome and reduce the degree of side effects, but it will not increase the risk of infection.

Efficacy and safety of metformin in combination with chemotherapy in cancer patients without diabetes: systematic review and meta-analysis.

Background: The results of a meta-analysis of retrospective studies suggest that the use of metformin in cancer patients may prolong progression-free disease survival and overall survival. However, the studies included in the meta-analysis did not strictly distinguish between patients with or without type 2 diabetes mellitus. Therefore, further studies are needed to assess whether the use of adjuvant chemotherapy with metformin in cancer patients without diabetes improves prognosis. Method: Systematic searches of Embase, Pubmed, and The Cochrane library were performed for the subject terms metformin and neoplasm and for free words. Data related to PFS, OS were extracted according to inclusion exclusion criteria. The data were combined and meta-analysis was performed using Review Manager 5.4 to confirm the efficacy and safety of metformin administration. Results: There were 3228 publications retrieved from the database and a total of 13 publications with 955 patients were included in the meta-analysis after screening. All included studies were randomised controlled trials. Metformin combined with adjuvant chemotherapy did not improve progression-free survival (HR=1,95CI 0.79-1.25), overall survival (HR=0.91,95% CI 0.69-1.20) and did not improve objective disease response rates in patients. There was no significant difference in grade 3-4 adverse reactions compared to placebo. Conclusion: In this meta-analysis of randomised controlled trial studies, we found that chemotherapy in combination with metformin in cancer patients without diabetes did not prolong progression-free survival and overall survival and improved disease control in patients, although there was no significant difference in terms of safety. More high-quality randomised controlled trials are needed in the future to confirm the in vivo anti-tumour activity and survival benefit of metformin.

TACE versus TACE + entecavir versus TACE + tenofovir in the treatment of HBV associated hepatocellular carcinoma.

BACKGROUND: At present, there are a variety of antiviral drugs for HBV in clinical practice, but there is no standard scheme for transcatheter arterial chemoembolization(TACE) combined with antiviral drugs. The aim of this study was to investigate whether TACE must be combined with antiviral therapy in patients of HBV-related hepatocellular carcinoma(HCC). Meanwhile, the efficacy and safety of TACE combined with entecavir and TACE combined with tenofovir in the treatment of HBV-related HCC were compared. METHOD: This study included 536 patients with HBV-related HCC who underwent TACE in Union Hospital from March 2017 to March 2020, and they met the criteria. They were divided into three groups: control group (N = 212): TACE alone; Entecavir group (N = 220): TACE combined with entecavir; and Tenofovir group (N = 228): TACE combined with tenofovir. We conducted a retrospective study to analyze the efficacy and safety of the three groups of patients. RESULTS: Objective response rate(ORR): 29.2% in control group, 54.1% in entecavir group, and 63.2% in tenofovir group (P < 0.05). Disease control rate(DCR): 63.7% in control group, 80.9% in entecavir group, and 88.1% in tenofovir group (P < 0.05). Median overall survival(mOS): control group, 12.2 months; entecavir group, 17.3 months; tenofovir group, 22.5 months (p < 0.05). Median progression-free survival (mPFS): control group, 9.3 months; entecavir group, 15.5 months; tenofovir group, 16.6 months (p < 0.05). At 6 months, there was an increase in creatinine(Cr) and a decrease in glomeruar filtration rate(GFR) in tenofovir group, which were statistically different from control and entecavir groups (p < 0.05). CONCLUSION: TACE combined with entecavir and TACE combined with tenofovir had higher ORR and DCR, longer OS and PFS than TACE alone. The OS of TACE combined with tenofovir was higher than that of TACE combined with entecavir. TACE combined with tenofovir is a safe strategy, but we cannot completely ignore the impact of tenofovir on renal function.

Efficacy and safety analysis of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced renal cell carcinoma: a retrospective study.

BACKGROUND: Since renal cell carcinoma(RCC) is insensitive to conventional chemoradiotherapy, molecularly targeted drugs are commonly used treatments for unresectable advanced RCC. The aim of this study was to explore the efficacy and safety of TACE + sunitinib vs. sunitinib in the treatment of unresectable advanced RCC. METHODS: This study included 98 patients with unresectable advanced RCC who were treated in Union Hospital from January 2015 to December 2018, and they met the criteria. They were divided into two groups: TACE + Sunitinib group (N = 47) and Sunitinib group (N = 51). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients. RESULTS: (1)TACE + Sunitinib group: 4 patients (8.5%) achieved CR, 27 patients (57.5%) achieved PR, 9 patients (19.1%) achieved SD, and 7 patients (14.9%) achieved PD. Sunitinib group, 0 patients (0%) achieved CR, 20 patients (39.2%) achieved PR, 14 patients (27.5%) achieved SD, and 17 patients (33.3%) achieved PD. (P = 0.017) (2)ORR: TACE + sunitinib group, 66.0%; sunitinib group, 39.2%. (P = 0.009) (3)DCR: TACE + sunitinib group, 85.1%; sunitinib group, 66.7%. (P = 0.038) (4) In the TACE + sunitinib group, mPFS was 15.6 months, mOS was 35.0 months; in the sunitinib group, the mPFS was 10.9 months, mOS was 25.7 months. (P < 0.001) (5) The incidence of abdominal pain, fever, and vomiting was higher in the TACE + sunitinib group than in the sunitinib group (abdominal pain: 55.3% vs. 13.7%; fever: 61.7% vs. 7.8%; vomiting: 40.4% vs. 19.6%; P < 0.05). The technical success rate of TACE in TACE + Sunitinib group is 100%. CONCLUSIONS: The TACE + sunitinib group had higher ORR and DCR, longer OS and PFS than the sunitinib alone group. TACE combined with sunitinib can play a complementary role and is a safe and effective treatment for advanced RCC.

A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis.

Intestinal epithelial cells (IECs) are implicated in the propagation of T-cell-mediated inflammatory diseases, including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD after allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver. IEC RIPK3 cooperates with RIPK1 to trigger mixed lineage kinase domain-like protein-independent production of T-cell-recruiting chemokines and major histocompatibility complex (MHC) class II molecules, which amplify and sustain alloreactive T-cell responses. Alloreactive T-cell-produced interferon gamma enhances this RIPK1/RIPK3 action in IECs through a JAK/STAT1-dependent mechanism, creating a feed-forward inflammatory cascade. RIPK1/RIPK3 forms a complex with JAK1 to promote STAT1 activation in IECs. The RIPK1/RIPK3-mediated inflammatory cascade of alloreactive T-cell responses results in intestinal tissue damage, converting the local inflammation into a systemic syndrome. Human patients with severe GVHD showed highly activated RIPK1 in the colon epithelium. Finally, we discover a selective and potent RIPK1 inhibitor (Zharp1-211) that significantly reduces JAK/STAT1-mediated expression of chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and arrests GVHD without compromising the graft-versus-leukemia (GVL) effect. Thus, targeting RIPK1/RIPK3 in IECs represents an effective nonimmunosuppressive strategy for GVHD treatment and potentially for other diseases involving GI tract inflammation.

Efficacy and Safety of Lobaplatin-TACE in the Treatment of Primary Hepatocellular Carcinoma: A Retrospective Study.

PURPOSE: To investigate the safety and efficacy of lobaplatin-TACE in treating primary hepatocellular carcinoma. METHODS: The data of 536 patients who underwent TACE in the interventional department from January 2016 to January 2020 were collected. Patients were divided into two groups according to the chemotherapeutic drugs used in TACE.: the epirubicin-TACE group (N = 260) and the lobaplatin-TACE group (N = 276). Primary study endpoint: (1) The tumor response after TACE; (2) The survival rates; Secondary study endpoints:(1) Changes in liver function and blood routine before and after TACE; (2) Occurrence of the post-embolization syndrome and infection after TACE. RESULTS: The ORR was 35.0% in the epirubicin-TACE group and 51.1% in the lobaplatin-TACE group (p=0.001). The DCR was 73.1% in the epirubicin-TACE group and 82.2% in the lobaplatin-TACE group (p=0.011). The 6-month, 9- month, 12-month, and 15-month survival rates were higher in the lobaplatin-TACE group than in the epirubicin-TACE group (p=0.029, p=0.001, p=0.005, p=0.002). mOS: Epirubicin-TACE group,14.8 months; Lobaplatin-TACE group,18.6 months (p=0.007). mPFS: Epirubicin-TACE group,9.5 months; Lobaplatin-TACE group,12.8 months (P =0.000). There was no statistical difference in ALT, AST, total bilirubin and Leucocyte after TACE between the two groups (p=0.343, p=0.368, p=0.288, p=0.359). The platelet decrease after TACE was more significant in the lobaplatin- TACE group than in the epirubicin-TACE group (p=0.046). There was no statistical difference in the incidence rate of abdominal pain, fever and infection after TACE between the two groups (p=0.502, p=0.602, p=0.726). The incidence of vomiting after TACE in the lobaplatin-TACE group was higher than that in the epirubicin-TACE group (p=0.003). CONCLUSION: Lobaplatin-TACE has a higher tumor response rate and survival rate. Lobaplatin-TACE is a safe and effective treatment strategy; it is worthy of clinical application.

Efficacy and safety of heparin plus dexamethasone after partial splenic embolization for liver cirrhosis with massive splenomegaly.

PURPOSE: The aim of this study was to investigate the efficacy and safety of the combination of low-molecular-weight heparin + dexamethasone after partial splenic embolization in cirrhotic patients with massive splenomegaly. METHODS: This study included 116 patients with liver cirrhosis complicated with massive splenomegaly who underwent PSE in Union Hospital from January 2016 to December 2019, and they met the criteria. They were divided into two groups: PSE + Hep + Dex group (N = 54) and PSE group (N = 62). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients. RESULTS: The volume of splenic embolization was 622.34 ± 157.06 cm3 in the PSE + Hep + DEX group and 587.62 ± 175.33 cm3 in the PSE group (P = 0.306). There was no statistically difference in the embolization rate of the spleen between the two groups (P = 0.573). WBC peaked 1 week after PSE and PLT peaked 1 month after PSE in both groups; it gradually decreased later, but was significantly higher than the preoperative level during the 12-month follow-up period. The incidences of abdominal pain (46.3% vs 66.1%, P = 0.039), fever (38.9% vs 75.8%, P < 0.001), PVT (1.9% vs 12.9%, P = 0.026), refractory ascites (5.6% vs 19.4%, P = 0.027) were lower in the PSE + Hep + DEX group than in the PSE group. The VAS score of abdominal pain in PSE group was higher than that in PSE + Hep + DEX group on postoperative days 2-8 (P < 0.05). Splenic abscess occurred in 1(1.6%) patient in the PSE group and none (0.0%) in the PSE + Hep + DEX group (P = 0.349). CONCLUSIONS: The combined use of dexamethasone and low-molecular-weight heparin after PSE is a safe and effective treatment strategy that can significantly reduce the incidence of complications after PSE (such as post-embolization syndrome, PVT, refractory ascites).

Graphene fibre film/polydimethylsiloxane nanocomposites for high-performance electromagnetic interference shielding.

Exploration of high-performance electromagnetic interference (EMI) shielding materials has become a trend to address the increasing electromagnetic (EM) wave pollution environment. In this paper, oriented graphene fibre film (GFF)/polydimethylsiloxane (PDMS) nanocomposites with one-ply unidirectional, two-ply cross-ply, and two-ply unidirectional configurations were prepared using wet-spinning and hot-pressing techniques in a two-step process. Due to the anisotropic electrical performance of GFF, the one-ply laminate exhibits EMI shielding anisotropy that is affected by fibre orientation relative to the electric field component in EM waves. The maximum shielding difference at 8.8 GHz is up to 32.0 dB between the fibre orientation parallel to and perpendicular to the electric field component. In addition, we found that adding a layer of GFF is an intuitive method to enhance the shielding efficiency (SE) of GFF/PDMS nanocomposites by providing more interfaces to enhance absorption losses. An optimal EMI shielding performance of a two-ply unidirectional laminate is observed with an SE value of 50.6 dB, which shields 99.999% of EM waves. The shielding mechanisms are also discussed and clarified from the results of both experimental and theoretical analyses by adjusting the GFF structural parameters, such as the fibre orientation, areal density, number of plies and stacking sequence.

A Comparative Analysis of Efficacy of Apatinib Combined with Transarterial Chemoembolization and Transarterial Chemoembolization Alone in the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Background: The treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains controversial due to the limited effect of sorafenib. The aim of the study was to investigate whether apatinib could improve the efficacy of transarterial chemoembolization (TACE) for patients with HCC complicated by PVTT. Methods: The study included 109 patients with HCC and PVTT who received TACE combined with apatinib (TACE + apatinib) (53 patients) or TACE alone (56 patients) between June 2015 and January 2019. Propensity score matching (PSM) analysis was used to reduce the potential selection bias. Overall survival time (OS) and time to progression (TTP) were used to evaluate the efficacy of TACE + apatinib and TACE alone. Results: Before PSM, TACE + apatinib significantly improved median TTP (7.0 vs. 3.0 months, P < 0.001) and median OS (15.0 vs. 7.0 months, P < 0.001) when compared with TACE alone. After PSM, the median TTP was significantly longer in the TACE + apatinib group, 6.0 months, than in the TACE alone group, 3.0 months (P < 0.001), and the median OS was significantly longer in the TACE + apatinib group, 14.0 months, than in the TACE alone group, 7.0 months (P < 0.001). Subgroup analysis revealed that, except for patients with Child-Pugh class B, the patients with or without extrahepatic metastases and with Child-Pugh class A had longer TTP and OS after the combined TACE + apatinib treatment than after TACE alone. Conclusion: The combination of TACE + apatinib might be an effective and safe treatment for HCC patients with PVTT.

Synthesis and characterization of potent RIPK3 inhibitors based on a tricyclic scaffold.

Background: Necroptosis is an important form of regulated cell death involved in inflammatory diseases, degenerative diseases and cancer. RIPK3 is an interesting target for intervention of necroptosis-associated diseases. Methodology: Herein the authors report the synthesis of a series RIPK3 inhibitors under the guidance of structure-based drug design which leads to the identification of compound 37. Results: Compound 37 potently rescued human and mouse cells from necroptotic stimuli TNF-α, Smac mimetic, z-VAD and LPS + z-VAD, displayed high affinity to RIPK3 (Kd = 14 nM) but no observable affinity to RIPK1 and inhibited RIPK3 kinase function. Importantly, compound 37 significantly alleviated TNF-induced systemic inflammatory response syndrome in the mouse model. Conclusion: These results support compound 37 as a prototype RIPK3 inhibitor for lead optimization.

Analysis of long-term effect of ureteral balloon dilatation combined with internal and external drainage tube in the treatment of benign ureteral stricture.

PURPOSE: There are few reports about balloon dilatation combined with internal and external drainage tube in the treatment of ureteral stricture under interventional therapy. The aim of the study is to explore the safety, effectiveness and long-term efficacy of this treatment strategy. MATERIALS AND METHODS: It is a retrospective and observational study. From October 2013 to October 2016, 42 patients with benign lower ureteral stricture received interventional treatment. Balloon dilatation combined with internal and external drainage tube implantation were used. There were 25 male patients and 17 female patients. There were 7 cases (16.7%) with congenital ureteral stricture, 12 cases (28.6%) with inflammation, 15 cases (35.7%) with ureteral stricture after lithotomy or lithotripsy, and 8 cases (19.0%) with ureteral stricture after pelvic or abdominal surgery. After the drainage tube was removed, B ultrasound, enhanced CTU or IVP of urinary system were reexamined every six months. The follow-up time was 12-60 months. RESULTS: The age was 52.9 ± 11.6 years. The length of ureteral stricture was 1.1 ± 0.5 cm. 42 patients completed interventional treatment, the technical success rate was 100%, no ureteral perforation, rupture or other complications were identified. Preoperative urea nitrogen 9.2 ± 2.3 mmol/L and creatinine 175.8 ± 82.8umol/L. Urea nitrogen and creatinine were 3.8-9.1 mmol/L and 45.2-189.6 umol/L when removing the drainage tube. There were significant differences in the levels of urea nitrogen and creatinine before and after tube removal (P < 0.05). The ureteral patency rate was 100% at 6 months, 93% at 12 months, 83% at 18 months, 79% at 24 months, 76% at 30 months and 73% at 36-60 months. The overall success rate was 73%. Multivariate Cox regression analysis showed that stenosis length was a risk factor for postoperative patency (P < 0.05). CONCLUSION: Balloon dilatation combined with internal and external drainage tube implantation in the treatment of benign lower ureteral stricture is safe and effective.

Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity.

RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, we report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 efficiently blocks necroptosis induced by TNFα in both human and mouse cells (EC50 = 17-30 nM). Biophysical assay demonstrates that compound 70 potently binds to RIPK1 (Kd = 9.2 nM), but not RIPK3 (Kd > 10,000 nM). Importantly, compound 70 exhibits greatly improved metabolic stability in human and rat liver microsomes compared to compound 6 (PK68), a RIPK1 inhibitor reported in our previous work. In addition, compound 70 displays high permeability in Caco-2 cells and excellent in vitro safety profiles in hERG and CYP assays. Moreover, pre-treatment of 70 significantly ameliorates hypothermia and lethal shock in SIRS mice model. Lastly, compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. Taken together, our work supports 70 as a potent RIPK1 inhibitor and highlights its potential as a prototypical lead for further development in necroptosis-associated inflammatory disorders.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE in the Third-Line Treatment of Colorectal Liver Metastases.

Background: The liver is the most common site of metastasis in colorectal cancer. In patients with unresectable colorectal liver metastases, the 5-year survival rate is less than 5%. Many patients with colorectal liver metastases require effective subsequent therapy after the failure of standard first-line/second-line therapy. The purpose of this study is to investigate the efficacy and safety of TACE combined with Regorafenib versus TACE in the third-line treatment of patients with colorectal liver metastases. Method: The clinical data of 132 patients with colorectal liver metastases were collected. There were two groups: TACE + Regorafenib group (N = 63); TACE group (N = 69). TACE uses CalliSpheres® drug-loaded microspheres (loaded with irinotecan). Regorafenib is administered at a dose of 120 mg once daily. If the patient is severely intolerable, the regorafenib dose is adjusted to 80 mg once daily. Primary study endpoints were (1) to evaluate the tumor response, ORR, and DCR and (2) to evaluate OS and PFS in the two groups. Secondary study endpoints were (1) to compare the performance status, CEA, CA19-9 after treatment between the two groups and (2) to compare the incidence of adverse events between the two groups. Results: There were significant differences in tumor response, ORR, DCR, OS, and PFS after treatment between the two groups. TACE combined with the Regorafenib group versus the TACE group: ORR (57.1% vs 33.3%), DCR (82.5% vs 68.1%), mOS (18.2 months vs 11.3 months), and mPFS (8.9 months vs 5.3 months). The performance status after treatment was better in the TACE + Regorafenib group than in the TACE group (P < 0.05). The CEA and CA19-9 negative rates after treatment were higher in the TACE + Regorafenib group than in the TACE group (P < 0.05). Conclusion: For the third-line treatment of colorectal liver metastases, the combination of TACE + Regorafenib had better tumor response, OS, and PFS than TACE TACE + Regorafenib combination could be considered as salvage therapy for colorectal liver metastases who failed the first- and second-line standard therapy.

Quantitative splenic embolization possible: application of 8Spheres conformal microspheres in partial splenic embolization (PSE).

BACKGROUND: To investigate the safety and efficacy of 8Spheres in partial splenic embolization. To explore the possibility of accurate control of splenic embolic volume by quantifying the number of microspheres used during PSE. METHOD: The data of 179 patients who underwent PSE were collected. The patients were divided into two groups: 300-500 um microsphere group (N = 83) and 500-700 um microsphere group (N = 96). The spleen volume before PSE, infarct volume and infarct rate of the spleen after PSE, changes in peripheral blood cells after PSE, postoperative adverse events and incidence of infection were compared between the two groups. RESULTS: 300-500 um group vs 500-700 um group: postoperative spleen volume (cm3): 753.82 ± 325.41 vs 568.65 ± 298.16 (P = 0.008); spleen embolization volume (cm3): 525.93 ± 118.29 vs 630.26 ± 109.71 (P = 0.014); spleen embolization rate: 41.1 ± 12.3% vs 52.4 ± 10.1% (P = 0.021). Leukocytes and platelets were significantly increased after PSE in both groups; leukocyte, 1 month: 4.13 ± 0.91 vs 5.08 ± 1.16 (P = 0.026); 3 months: 4.08 ± 1.25 vs 4.83 ± 0.98 (P = 0.022); platelet, 1 month: 125.6 ± 20.3 vs 138.7 ± 18.4 (P = 0.019); 3 months: 121.8 ± 16.9 vs 134.3 ± 20.1 (P = 0.017). Incidence of abdominal pain after PSE, 72 (86.7%) vs 69 (71.9%), P = 0.027. The incidence of other adverse events and infections after PSE was not statistically different. CONCLUSION: PSE with 8Spheres is safe and effective. The use of 500-700 um microsphere for PSE can make the increase of peripheral blood cells more stable. Each vial of 8Spheres corresponds to a certain volume of splenic embolization, so it is possible to achieve quantitative embolization in PSE.

Efficacy and safety analysis of dexamethasone-lipiodol emulsion in prevention of post-embolization syndrome after TACE: a retrospective analysis.

BACKGROUND: To investigate the efficacy and safety of dexamethasone-lipiodol emulsion in the prevention of post-embolization syndrome after TACE. METHOD: The data of 255 patients who underwent TACE in the interventional department from June 2017 to June 2020 were collected. This is a retrospective assessment of patients who were non-randomly treated with dexamethasone in TACE. The patients were divided into two groups: TACE using lipiodol + chemotherapeutic emulsion group (TACE group, N = 133); TACE using lipiodol + dexamethasone + chemotherapeutic emulsion group (TACE + dexamethasone group, N = 122). Primary study endpoint: incidence of abdominal pain, fever, nausea and vomiting 0-72 h after TACE in both groups. Secondary study endpoints: incidence of infection after TACE in both groups. RESULTS: Incidence of post-embolization syndrome after TACE (TACE group vs TACE + dexamethasone group): abdominal pain, 55.6% versus 36.1% (P value 0.002); fever, 37.6% versus 13.1% (P value 0.000); nausea, 60.9% versus 41.0% (P value 0.001); vomiting, 48.1% versus 21.3% (P value 0.000). Incidence of infection after TACE (TACE group vs TACE + dexamethasone group): 1.5% versus 2.5% (P value 0.583). CONCLUSION: The lipiodol + dexamethasone emulsion can significantly reduce the incidence rate of post-embolization syndrome after TACE, with exact effect and high safety.