High-dose oxaliplatin induces severe hypersensitivity reactions and high recurrence rates during rechallenge in patients treated with hepatic arterial infusion chemotherapy.

AIM: To analyze the risk factors for oxaliplatin (OXA)-induced severe hypersensitivity reactions and identify the recurrence rate of the reactions after an OXA rechallenge in patients treated with hepatic arterial infusion chemotherapy (HAIC). METHODS: Among the 2251 patients treated with HAIC (OXA), 84 patients with gastrointestinal cancer who displayed hypersensitivity reactions between May 2013 and May 2022 were included in this study. Among the 84 patients, 23 (27.4%) developed severe anaphylactic reactions (grade III/IV), and 61 (72.6%) developed grade I/II reactions. We explored the risk factors for severe OXA-induced hypersensitivity reactions. Twenty-seven patients with grade I/II reactions underwent retreatment (HAIC with OXA), and the recurrence rate of the hypersensitivity reactions was determined. A multivariate logistic regression model was used to analyze the risk factors for OXA-induced hypersensitivity reaction. RESULTS: In the study, multivariate analysis indicated that the dose of OXA (odds ratio [OR] 3.077, 95 % confidence interval [CI] 1.106-8.558, p = 0.031) was an independent risk factor for OXA-induced severe hypersensitivity reactions. Twenty-seven patients with non-severe hypersensitivity reactions underwent retreatment HAIC with OXA and 14 (51.9 %) experienced HSR recurrence, including 2 (7.4 %) who experienced hypersensitivity shock. CONCLUSIONS: The administration of OXA doses is a risk factor for OXA-induced severe hypersensitivity reactions in patients treated with HAIC (OXA). Rechallenging HAIC with OXA appears to be associated with a higher recurrence rate of the HSR.

Efficacy and Safety of HepaSphere Drug-Eluting Bead Transarterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy as the Second-Line Treatment in Advanced Hepatocellular Carcinoma.

Purpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC. Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.

A Novel Nomogram for Predicting the Overall Survival in Patients with Unresectable HCC after TACE plus Hepatic Arterial Infusion Chemotherapy.

BACKGROUND AND AIM: Transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) has shown encouraging efficacy in the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict overall survival (OS) of patients with unresectable HCC treated with TACE-HAIC. METHODS: A total of 591 patients with unresectable HCC treated with TACE-HAIC between May 2009 and September 2020 were enrolled. These patients were randomly divided into training and validation cohorts. The independent prognostic factors were identified with Cox proportional hazards model. The model's discriminative ability and accuracy were validated using concordance index (C-index), calibration plots, the area under the time-dependent receiver operating characteristic curve (AUC) and decision curve analyses (DCAs). RESULTS: The median OS was 15.6 months. A nomogram was established based on these factors, including tumor size, vein invasion, extrahepatic metastasis, tumor number, alpha fetoprotein (AFP), and albumin-bilirubin (ALBI), to predict OS for patients with unresectable HCC treated with TACE-HAIC. The C-index of the nomogram were 0.717 in the training cohort and 0.724 in validation cohort. The calibration plots demonstrated good agreement between the predicted outcomes and the actual observations. The AUC values were better than those of three conventional staging systems. The results of DCA indicated that the nomogram may have clinical usefulness. The patients in the low-risk group had a longer OS than those in intermediate-risk and high-risk groups (P<0.001). CONCLUSION: A prognostic nomogram was developed and validated to assist clinicians in accurately predicting the OS of patients with unresectable HCC after TACE-HAIC.

Effect of Different Temperatures on the Hydration Kinetics of Urea-Doped Cement Pastes.

Urea can solve the problem of concrete cracking due to temperature stress. However, its effect is affected by temperature. The influencing mechanism of temperature on urea-doped cement pastes is still unclear. This paper explores the effect of different temperatures on the hydration kinetics of urea-doped cement pastes. The isothermal calorimeter (TAM Air) was used to test hydration at three constant temperatures (20 °C, 40 °C, and 60 °C). The effects of the urea admixture and temperature on the hydration process and hydration kinetics parameters were investigated. The hydration mechanism was analyzed, and the changes in macroscopic mechanical compressive strength and porosity were tested. The results show that, as the urea content (UC) increases, the rate of hydration gradually decreases, and the increase in temperature promotes the inhibitory effect of urea. At 60 °C, UC of 8% can be reduced by 23.5% compared with the pure cement (PC) group's hydration rate. As the temperature increases from 20 °C to 60 °C, the Krstulovic-Dabic model changes from the NG-I-D process to the NG-D process. The effect of urea on the compressive strength of the cement is mainly shown in the early stage, and its effect on later strength is not obvious. In addition, urea will increase its early porosity. The porosity will gradually decrease in the later stage. The results of the study clarify the effect of temperature on urea-doped cement pastes. The optimal content of urea in cement is about 8%, which will provide theoretical guidance for solving the cracking problem of large-volume concrete due to temperature stress.

A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases.

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02557490.

Microglial Responses and Pain Behaviors Are Exacerbated by Chronic Sleep Deprivation in Rats with Chronic Pain Via Neuroinflammatory Pathways.

The inflammatory response of central nervous system (CNS) and microglial activation is important in the development of pain behaviors induced by sleep deprivation. We found that chronic sleep deprivation (CSD) aggravated pain behaviors in rats with chronic pain by upregulating expression of Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), and interleukin 1ß (IL-1ß), which promoted microglial activation in the brain. We also found that CSD increased numbers of Iba1+ and TLR4+ cells, as well as neuronal apoptosis. Inhibitors of TLR4 and NLRP3 (TAK-242 and MCC950, respectively) reduced expression levels of inflammatory factor proteins and M1-related factor mRNA, decreased microglial activation, and relieved the hyperalgesia caused by CSD. These results suggest that CSD aggravated pain behavior in rats with chronic pain through the TLR4/NLRP3/IL-1ß signaling pathway, which mediates microglial activation and promotes CNS inflammation and neuronal apoptosis.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors for advanced hepatocellular carcinoma.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0-24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe.

Lay abstract Some tyrosine kinase inhibitors (TKIs) that inhibit tumor vessel growth, such as sorafenib and lenvatinib, have been recommended as first-line treatment for advanced hepatocellular carcinoma (HCC). In hepatic artery infusion chemotherapy, chemotherapeutic drugs can be delivered via a microcatheter to the tumor-supplying artery to increase the local drug concentration, leading to higher local disease control rates and less toxicity than systemic chemotherapy. The combination of anti-PD-1 immunotherapy plus TKIs was shown in a previous study to be a safe and effective treatment for advanced HCC. This study explored the safety and effectiveness of hepatic artery infusion chemotherapy, TKIs and an anti-PD-1 antibody for the treatment of advanced HCC and found that combination therapy is effective, with good tolerability.

Combination Therapy of Chemoembolization and Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Compared with Chemoembolization Alone: A Propensity Score-Matched Analysis.

BACKGROUND: Survival of patients with portal vein tumor thrombosis (PVTT) is extremely poor; transarterial chemoembolization (TACE) is a treatment for patients with HCC and PVTT. Some studies showed that hepatic arterial infusion chemotherapy (HAIC) might improve the survival of HCC with PVTT. There were few researches of combining TACE with HAIC for patients with HCC and PVTT. AIM: This study was aimed at comparing overall survival (OS) and progression-free survival (PFS) following treatment with conventional transarterial chemoembolization plus hepatic arterial infusion chemotherapy (cTACE-HAIC) or conventional transarterial chemoembolization (cTACE) alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHODS: From January 2011 to December 2016, 155 patients with HCC and PVTT who received cTACE-HAIC (cTACE-HAIC group) (n = 86) or cTACE alone (cTACE group) (n = 69) were retrospectively evaluated. Propensity score matching (PSM) reduced the confounding bias and yielded 60 matched patient pairs. The tumors' responses were evaluated using the modified response evaluation criteria in solid tumors (mRECIST). OS and PFS of groups were compared using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models. RESULTS: The median follow-up duration was 93 months (range: 1-93 months). The cTACE-HAIC group's OS (9.0 months) and PFS (6.0 months) were significantly longer than the cTACE group's OS (5.0 months) and PFS (2.0 months) (p = 0.018 and p = 0.045, respectively) in the matched cohort. Multivariate analyses showed that cTACE-HAIC was independently associated with OS (hazard ratio (HR) 0.602, p = 0.010) and PFS (HR 0.66, p = 0.038). The matched groups did not differ regarding grade 3 or 4 adverse events. CONCLUSION: cTACE-HAIC was superior to cTACE alone regarding OS and PFS in patients with HCC and PVTT. Treatment-associated toxicities were generally well tolerated.

Remifentanil preconditioning alleviates myocardial ischemia/reperfusion injury in rats via activating Jagged-1/Notch signaling pathway.

Ischemic heart diseases have emerged as great threats to human health. Nowadays, restoration of cardiac blood flow supply is widely regarded as a feasible treatment choice for ischemic heart diseases; however, this intervention would contradictorily elicit reperfusion injury. Recently, myocardial ischemia/reperfusion injury (MI/RI) has aroused widespread public concerns. Remifentanil, an ultra-short acting opioid analgesic, is frequently used for surgical anesthesia. Previous studies have demonstrated the cardioprotective effects of remifentanil preconditioning in clinical practice and in vitro experimental models; however, its exact mechanisms remain largely unclear. This study aimed to further evaluate the protective effects of remifentanil preconditioning against MI/RI and elucidate the potential molecular mechanisms. Rat models of MI/RI were successfully established via ligation of left anterior descending coronary artery for 30 minutes and restoration of blood flow for 2 hours. Herein, animal experiments displayed that remifentanil preconditioning could alleviate myocardial damage in rat models of MI/RI. Consistently, cell model experiments implied that remifentanil preconditioning attenuated hypoxia/reoxygenation exposure-induced injury in rat cardiomyocytes. Moreover, our findings verified the involvement of Notch signaling pathway in the protective effects of remifentanil preconditioning. In addition, mechanistic studies revealed that remifentanil preconditioning could up-regulate Jagged-1 expression and that Jagged-1 mediated the cardioprotective effects of remifentanil preconditioning through activating Notch signaling pathway. Taken together, our data indicate that remifentanil preconditioning ameliorates myocardial damage in rat MI/RI models via Jagged-1-mediated Notch signaling pathway activation. Thus, this study may offer some novel clues for understanding the cardioprotective mechanisms of remifentanil preconditioning against MI/RI.

γ-Glutamyltranspeptidase as a Prognostic Biomarker in Advanced Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

PURPOSE: To evaluate the prognostic value of pretreatment serum γ-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization. MATERIALS AND METHODS: This retrospective study included 140 patients (123 male, 17 female; mean age, 56.9 y ± 12.0; range, 22.0-82.0 y) with Barcelona Clinic Liver Cancer class C HCC who received first-line conventional chemoembolization between December 2013 and March 2018. Patients were divided into low and high GGT groups based on a cutoff value calculated with a receiver operating characteristic curve. Overall survival (OS) was compared between groups by log-rank test. Univariate and multivariate survival analyses were performed. RESULTS: The optimal cutoff values of GGT were 119.5 U/L in men and 175.0 U/L in women. The 6-, 9-, and 12-mo OS rates were 81.7%, 72.4%, and 62.9%, respectively, for patients in the low GGT group (n = 44) and 58.8%, 35.7%, and 28.8%, respectively, for patients in the high GGT group (n = 96; P < .001). Multivariable Cox regression analysis identified high pretreatment serum GGT level (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.67-4.40; P < .001), multiple tumors (HR, 3.05; 95% CI, 1.23-7.53; P = .02), and performance of target treatment (ie, sorafenib; HR, 0.41; 95% CI, 0.24-0.72; P = .002) or ablation (HR, 0.35; 95% CI, 0.18-0.66; P = .001) as independent prognostic factors for OS. CONCLUSIONS: Pretreatment serum GGT level was an independent prognostic factor for OS in patients with advanced HCC treated with chemoembolization, suggesting that GGT is a useful prognostic biomarker for advanced HCC.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC. AIM: To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC. METHODS: In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety. RESULTS: In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4-58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1-54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4-58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4-54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups. CONCLUSION: No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

SIRT4 suppresses the inflammatory response and oxidative stress in osteoarthritis.

Sirtuins have been involved in the osteoarthritis (OA) process. However, the functions of SIRT4 in the degeneration of human chondrocytes and OA are not fully understood. This study aimed to explore the role of SIRT4 during OA and mechanisms implicated. We extracted total protein and mRNA of the cartilage from OA patients and isolated the chondrocytes from the cartilage in different degenerated degrees for cell culture. Collagen II and SIRT4 levels of the tissues were analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot. Chondrocytes were transferred with SIRT4-siRNA, treated with recombinant human SIRT4 protein for 24 h, respectively. Aggrecan, collagen I, collagen II, MMP-13, IL-6, TNF-α, SOD1, SOD2, and CAT expression, and ROS levels were investigated by Western blot, RT-PCR, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), or flow cytometry. Collagen II decreased significantly in severely degenerated cartilage compared to the mild one, paralleling with SIRT4 expression both in protein and mRNA levels. Chondrocytes in severe OA grade were observed with a decrease in aggrecan, collagen II, SOD1, SOD2, CAT expression, nonetheless, an increase in collagen I, reactive oxygen species (ROS), MMP-13, IL-6, and TNF-α levels. However, SRIT4 protein treatment significantly upregulated aggrecan, collagen II, an antioxidant enzyme, and suppressed ROS and inflammatory response. Further analysis revealed that silencing of SIRT4 expression induced healthy chondrocytes, a decrease in aggrecan, collagen II and antioxidant enzyme expression, and an increase in ROS and inflammatory response, importantly, which can be reversed by SIRT4 protein stimuli. Our results elucidated that SIRT4 was tangled with the development of OA, and SIRT4 overexpression contributes to suppresses the inflammatory response and oxidative stress.

Clinical Efficacy of Ultrasound-Mediated Transdermal Lidocaine and Capsaicin Delivery for the Treatment of Allodynia Caused by Herpes Zoster.

OBJECTIVE: To investigate the efficacy of ultrasound-mediated drug delivery for allodynia caused by herpes zoster. DESIGN: Unblinded randomized controlled study with two treatment groups and an additional control group. SUBJECTS: Patients hospitalized with allodynia caused by herpes zoster were enrolled. METHODS: Patients were randomly assigned to three groups: ultrasound-mediated transdermal drug delivery (group U), lidocaine intradermal injection (group I), or control group (group C). The primary outcome was pain intensity associated with allodynia, assessed with the visual analog scale (VAS) while brushing the skin with clothing after treatment stimulated allodynia. The secondary outcomes included an emotional functioning score (ES), average gabapentin consumption, and incidence of adverse events of each group. RESULTS: Sixty patients were enrolled in the study, but two of them failed to complete the treatment process. Therefore, 58 patients were included in the final analysis. All groups had lower VAS and ES scores after treatment compared with baseline. The VAS scores in groups U and I decreased significantly more than in group C (P < 0.05). Mean VAS scores in group U on days 1, 2, and 3 were lower than in group C (P < 0.01). ES was significantly lower in group U compared with groups I and C after treatment (P < 0.001). Average gabapentin consumption and incidence of adverse events in group C were higher than in the other two groups. CONCLUSIONS: In this study of treatment of allodynia caused by herpetic zoster, ultrasound-mediated lidocaine and capsaicin delivery provided better pain relief and improved emotional functioning compared with intradermal blockade with local anesthetics.

Parecoxib exhibits anti-inflammatory and neuroprotective effects in a rat model of transient global cerebral ischemia.

Transient global cerebral ischemia (tGCI) induces inflammation leading to secondary brain injury. Data suggested that cyclooxygenase-2 (COX-2) is involved in the occurrence and development of inflammatory reaction after reperfusion; however, the effectiveness of a highly selective COX-2 inhibitor, parecoxib, to counteract tGCI remains to be determined. Thus, the aim of this study was to investigate the potential protective actions of parecoxib in a rat model of tGCI and the role inflammation plays in this disorder. Adult male Sprague-Dawley rats were administered parecoxib 10 or 20 mg/kg intraperitoneally (ip) at 5 min, 24 or 48 hr after tGCI. Control rats received an equal volume of 0.9% saline. The rat model of tGCI was established using the method of bilateral common carotid artery occlusion combined with arterial hypotension. The following parameters were measured: Neurological Severity Score, morphological changes in the hippocampal CA1 region, Evans blue (EB) extravasation, brain water content, levels of matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), neuronal apoptosis, the protein expression of Bcl-2, Bax, COX-2, prostaglandin E2 (PGE2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Parecoxib treatment significantly improved neurological function and morphological defects in the hippocampal CA1 region, reduced levels of COX-2, PGE2, IL-1ß, and TNF-α. In addition, parecoxib attenuated brain edema and BBB destruction as evidenced by increased ZO-1 expression and decreased MMP-9 expression. Further, parecoxib reduced neuronal apoptosis via diminished protein expression of Bax and enhanced expression of Bcl-2.

Safety and efficacy of hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin post-transarterial chemoembolization for unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the safety, efficacy, and prognostic factors of hepatic arterial infusion chemotherapy (HAIC) with raltitrexed and oxaliplatin post-transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC). METHODS: Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). The overall response rate (ORR) was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v4.0). The OS and prognostic factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression models. RESULTS: Three (8.1%) patients achieved complete response, 17 (46.0%) patients achieved partial response, and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months, respectively. The common toxicities included grade 3-4 increased aspartate aminotransferase levels (8/37,21.6%), grade 1-2 hyperbilirubinemia (75.7%, 28/37), nonspecific abdominal pain and fever, and grade 2-3 thrombocytopenia (18.9%, 7/37); no patients developed grade 3-4 neutropenia. Univariate analysis showed that the tumor diameter (≤50 mm, p = 0.028), Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.012), hepatitis B virus DNA level (p = 0.033), and derived neutrophil-to-lymphocyte ratio (dNLR; derived neutrophils/leukocytes minus neutrophils) (p = 0.003) were predictive factors for prognosis. Multivariate analysis showed that patients with BCLC stage B disease (p = 0.029) and dNLR≤2 before therapy (p = 0.004) had better prognosis. CONCLUSIONS: HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC; in particular, those with BCLC stage B and dNLR≤2 have better prognosis.

Preliminary clinical efficacy of iodine-125 seed implantation for the treatment of advanced malignant lung tumors.

AIMS: This study aims to observe the preliminary clinical efficacy of percutaneous interstitial brachytherapy using iodine-125 seeds for the treatment of advanced malignant lung tumors. SUBJECTS AND METHODS: This retrospective study enrolled 24 patients in our hospital with advanced malignant lung tumors between June 2013 and November 2017. Computed tomography (CT)-guided iodine-125 seed implantation therapy was administered to these patients. All patients were followed up at 3, 6, and 12 months after the operation. The clinical efficacy was evaluated by CT. RESULTS: Among the 24 patients, the objective response rates at 3, 6, and 12 months after the procedure were 50.0%, 50.0%, and 33.3%, respectively. Recent occurrence of adverse reactions were observed, including four cases of pneumothorax, three cases of hemoptysis, and two cases of particle displacement. CONCLUSIONS: CT-guided percutaneous interstitial brachytherapy with iodine-125 seeds can be used for the treatment of lung malignant tumors. Its clinical curative effect is remarkable and it results in limited trauma, reducing the incidence of adverse reactions and improving patient quality of life.

MiR-155 modulates the progression of neuropathic pain through targeting SGK3.

This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR-155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment.