Transarterial chemoembolization combined with apatinib versus transarterial chemoembolization alone for hepatocellular carcinoma with macroscopic vascular invasion: A propensity score matching analysis

Context: Macroscopic vascular invasion in hepatocellular carcinoma (HCC) remains challenging to treat. Aims: The aim of this study was to compare the efficacy of transarterial chemoembolization (TACE)–apatinib therapy with TACE treatment alone in HCC patients with macrovascular invasion, using propensity score matching (PSM). Settings and Design: Matched paired comparison between the TACE–apatinib and TACE alone group using 1:2 PSM was utilized. Subjects and Methods: Between 2013 and 2019, 378 patients receiving TACE–apatinib or TACE alone were included based on specific selection criteria. Statistical Analysis Used: Multivariate Cox regression models were used to determine the independent prognostic factors for overall survival (OS). Results: Of the patients included, 40 (12.5%) received TACE–apatinib treatment and 280 (87.5%) received TACE alone. Tumor sizes of patients in the TACE–apatinib group were more frequently classified as small (<5 cm) compared to those in the TACE alone group (P = 0.021; mean: 8.6 cm vs. 10.2 cm). After 1:2 PSM, 40 pairs of HCC patients with well-matched covariates were selected from the two treatment groups. Patients in the TACE–apatinib group had higher OS rates than patients in the TACE alone group (P = 0.018). The median OS times were 18.2 and 8.5 months in the TACE–apatinib and TACE alone groups, respectively. The OS hazard ratio for the choice of TACE–apatinib treatment compared to TACE treatment alone was 0.50 (95% confidence interval: 0.28–0.90; P = 0.021). Conclusions: TACE combined with apatinib may result in superior OS compared to TACE therapy alone for HCC patients with macrovascular invasion

Biosynthetic L-tert-leucine using Escherichia coli co-expressing a novel NADH-dependent leucine dehydrogenase and a formate dehydrogenase

BACKGROUND: L-tert-Leucine has been widely used in pharmaceutical, chemical, and other industries as a vital chiral intermediate. Compared with chemical methods, enzymatic methods to produce L-tert-leucine have unparalleled advantages. Previously, we found a novel leucine dehydrogenase from the halophilic thermophile Laceyella sacchari (LsLeuDH) that showed good thermostability and great potential for the synthesis of L-tertleucine in the preliminary study. Hence, we manage to use the LsLeuDH coupling with a formate dehydrogenase from Candida boidinii (CbFDH) in the biosynthesis of L-tert-leucine through reductive amination in the present study. RESULT: The double-plasmid recombinant strain exhibited higher conversion than the single-plasmid recombinant strain when resting cells cultivated in shake flask for 22 h were used. Under the optimized conditions, the double-plasmid recombinant E. coli BL21 (pETDute-FDH-LDH, pACYCDute-FDH) transformed 1 mol·L-1 trimethylpyruvate (TMP) completely into L-tert-leucine with greater than 99.9% ee within 8 h. CONCLUSIONS: The LsLeuDH showed great ability to biosynthesize L-tert-leucine. In addition, it provided a new option for the biosynthesis of L-tert-leucine.

Transcatheter arterial infusion of anti-programmed cell death 1 antibody pembrolizumab combined with temozolomide or nab-paclitaxel in patient with primary anorectal malignant melanoma: Four case reports

Primary anorectal malignant melanoma (ARMM) is an extremely rare but aggressive tumor. We assessed the efficacy and safety of transcatheter arterial infusion (TAI) with anti-PD-1 antibody pembrolizumab at a dosage of 100 mg with 0.9% NaCl at a volume of 100 mL administered over a 30-min period every 3 weeks, combined with temozolomide or albumin-bound paclitaxel (nab-paclitaxel) in four patients with ARMM. Temozolomide was administered orally once per day at a dosage of 200 mg/m2/d for five consecutive days about every 4 weeks. Nab-paclitaxel was administered at a dosage of 200mg/m2/d once about every 3 weeks. Among four patients with a median follow-up of 8.9 months, two cases showed Murine Double Minute 2 (MDM2) amplification. Case 1 with Stage II ARMM showed pathological complete response after four cycles of TAI with pembrolizumab combined with nab-paclitaxel. Case 4 was at Stage II and showed stable disease consistently throughout the treatment. Case 2 was at stage II and Case 3 was at stage III, and they showed partial response after four or three cycles, respectively, of TAI with pembrolizumab combined with temozolomide. No Grades 3–4 adverse reactions were observed. Therefore, a combination of TAI with pembrolizumab and temozolomide or with nab-paclitaxel appears to be a promising option for treating ARMM. However, multicenter clinical trials are required to confirm the efficacy and safety of this procedure

Transarterial chemoembolization combined with microwave ablation and apatinib in patients with Barcelona clinic liver cancer Stage C hepatocellular carcinoma: A propensity score matching analysis

Context and Aims: Apatinib combined with transarterial chemoembolization (TACE) has shown promising results in cases of Barcelona clinic liver cancer Stage C (BCLC C) hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of TACE in combination with microwave ablation (MWA) and apatinib. Materials and Methods: A retrospective, single.center study was undertaken using a one.to.one propensity score matching (PSM) analysis design and involved BCLC C HCC patients who underwent treatment with TACE.MWA.apatinib or TACE alone between January 2013 and June 2018. The patients were recommended to administer 500mg apatinib per day, combined with MWA and TACE. The adverse effects of apatinib, MWA. and TACE.related complications, progression.free survival (PFS), and overall survival (OS) were assessed. Results: Of the 149 patients with BCLC C HCC who underwent TACE.MWA.apatinib or TACE alone, 131 were included in our study. Among them, 21 (16.0%) received TACE.MWA.apatinib and 110 (84.0%) underwent TACE alone. After PSM, twenty pairs were enrolled into different treatment groups. Patients in the TACE.MWA.apatinib group had a significantly longer median PFS than patients in the TACE.alone group on both before (median, 8.9 vs. 1.7 months, P = 0.0002) and after PSM (median, 5.4 vs. 2.1 months, P = 0.001). They also had a significantly longer median OS than patients in the TACE.alone group on before (median, 24.4 vs. 5.8 months, P = 0.000007) and after PSM (median, 24.4 vs. 5.4 months, P = 0.00005). Conclusions: The combination of apatinib, TACE, and MWA in BCLC C HCC patients is safe and effective. Toxicity is manageable by adjusting the apatinib dosage

Melanoma liver metastases with special imaging features on magnetic resonance imaging after microwave ablations: How to evaluate technical efficacy?

Purpose: To evaluate the technical feasibility of microwave ablation (MWA) for melanoma liver metastases with persistent high signal on magnetic resonance imaging (MRI). Materials and Methods: Seven patients with 22 target melanoma liver metastases who underwent MWA treatment were included. All procedure-related complications were observed and recorded. One month after MWA, the imaging features of treated liver metastases and ablation zones with different MRI sequences were reviewed to evaluate technique efficacy. To verify the correctness of the evaluation, MRI scans during patient follow-up were reviewed and compared with images before MWA to analyze changes in treated liver metastases and ablation zones. Results: All ablations were performed successfully, and there were no procedure-related major complications. After ablation, according to MRI T1-weighted pre-contrast or contrast sequences, the persistence of high signals from the treated lesions was noted inside the ablation zones of 19 lesions. Among these 19 lesions, 17 were completely covered by the ablation zones and were considered successfully treated, whereas two lesions were not completely covered and were considered unsuccessfully treated. Three lesions could not be detected on any MRI sequence after ablation and were also considered successfully treated. Finally, MRI scans during patient follow-up care verified these evaluations. Conclusion: MWA is a technically feasible option for melanoma liver metastases with special imaging features on MRI

Long noncoding RNA FOXD2-AS1 incuced gastric cancer cell MGC-803 to apatinib resistance by regulating miR-185-5p/CCND2 modulating axis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the molecular mechanism of lncRNA FOXD2-AS1 participating in apatinib resistance in gastric cancer cells by regulating miR-185-5p/CCND2 axis. Methods: The gastri cancer tissues and corresponding paracancerous tissues of 25 patients with gastric cancer were collected from April 2016 to December 2017 in the Fifth People’s Hospital of Wuxi City. The expressions of FOXD2-AS1, miR-185-5p, and cyclin D2 (CCND2) in gastric cancer tissues or cell lines were examined by quantitative realtime polymerase chain reaction (qRT-PCR). CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay were applied to assess the sensitivity of gastric cancer cells to apatinib. The interaction between FOXD2-AS1, miR-185-5p and CCND2 was explored by dual luciferase reporter gene assay, which was then confirmed by qRT-PCR, and Western blotting. Results: FOXD2-AS1 was highly expressed in gastric cancer tissues and apatinib-resistant gastric cancer cells. Over-expression of FOXD2-AS1 promoted apatinib-resistance of MGC-803/AP cells. Dual luciferase reporter gene assay confirmed that FOXD2-AS1 directly interacted with miR-185-5p and suppressed its expression. miR-185-5p significantly abolished the promotion effect of FOXD2-AS1 on apatinibresistance via inhibiting cell proliferation, invasion and promoting apoptosis of gastric MGC-803/AP cells. miR-185-5p could negatively regulate CCND2 expression; and FOXD2-AS1 promoted the cell proliferation, invasion and inhibited apoptosis of MGC-803/AP cells via down-regulating the inhibition effect of miR-185-5p on CCND2, thus further enhanced the apatinib-resistance of gastric cancer cells. Conclusion: FOXD2-AS1 induced apatinib-resistance of gastric cancer cells by regulating miR-185-5p/CCND2 axis.

Prolonged delirium misdiagnosed as a mood disorder / Delirium prolongado diagnosticado como transtorno de humor

ABSTRACT Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

RESUMO Delirium pode ser conceituado como o declínio agudo na função cognitiva que geralmente dura de horas a dias. O delírio prolongado também pode afetar pacientes com múltiplos fatores predisponentes e/ou precipitantes. Na prática clínica, o delírio prolongado é muitas vezes não reconhecido, e pode ser diagnosticado como outros transtornos psiquiátricos. Aqui, descrevemos o caso de um homem de 59 anos apresentando sintomas comportamentais e cognitivos que foi diagnosticado inicialmente com transtorno de humor em um hospital geral. Após ser diagnosticado delirium prolongado devido a múltiplos fatores, o paciente foi tratado de acordo, evoluindo com melhora progressiva do seu estado clínico. O diagnóstico e o manejo precoces do delirium prolongado são importantes para melhorar o prognóstico do paciente e evitar medidas iatrogênicas.

Inhibition of Glial Activation in Rostral Ventromedial Medulla Attenuates Mechanical Allodynia in a Rat Model of Cancer-induced Bone Pain / 华中科技大学学报（医学）（英德文版）

Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP).Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry,but so far the mechanisms are poorly known.In this study,we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model.CIBP rats showed significant activation of microglia and astrocytes,and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β,IL-6,TNF-a and brain-derived neurotrophic factor) in the RVM.Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats' RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner.RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia,reversed the associated up-regulation of pro-inflammatory mediators and significantly attenuated mechanical allodynia.Taken together,these results suggest that RVM glial activation is involved in the pathogenesis of CIBP.RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators,which contribute to the descending facilitation of CIBP.