Activity in projection neurons from prelimbic cortex to the PVT is necessary for retrieval of morphine withdrawal memory.

Previous work has shown that the paraventricular nucleus of the thalamus (PVT) is an important region that is involved in the conditioned context-induced retrieval of morphine withdrawal memory. However, the upstream neural circuits that activate the PVT to participate in the conditioned context-induced retrieval of morphine withdrawal memory remain unknown. In the present work, we find that the conditioned context activates projection neurons from the prelimbic cortex (PrL) to the PVT, and the inhibition of PrL-PVT projection neurons inhibits the conditioned context-induced retrieval of morphine withdrawal memory; the conditioned context induces an increase in Arc expression, intrinsic excitability, and glutamate output in PrL-PVT projection neurons in morphine-withdrawn mice. These results suggest that the activity of PrL-PVT projection neurons is necessary for the retrieval of morphine withdrawal memory, and the conditioned context causes a plastic change in the activity in these projection neurons during the withdrawal memory retrieval.

Programmed cell death-ligand 1 expression in hepatocellular carcinoma and its correlation with clinicopathological characteristics.

BACKGROUND AND AIM: Programmed cell death-ligand 1 (PD-L1) immunohistochemistry score has been approved as the predictive biomarker for anti-PD1/PD-L1 therapy in several advanced malignancies. Although its predictive role remained inconclusive in hepatocellular carcinoma, ongoing study of anti-PD1/PD-L1 therapy showed promising results. However, less is known about the PD-L1 immunohistochemistry score and factors correlated with it in hepatocellular carcinoma. We investigated PD-L1 immunohistochemistry scores in a large cohort of hepatocellular carcinoma, as well as its correlation with various clinical and genomic factors. METHODS: Immunohistochemistry was performed to detect the expression of PD-L1 protein in 315 hepatocellular carcinoma tissues. All slides were independently reviewed by three senior pathologists. Next-generation YS panel (450 genes) sequencing was performed on 309 patients. RESULTS: Higher PD-L1 expression as measured by combined positive score (CPS) was associated with increased Edmondson-Steiner grade (grade III vs II, P = 0.041) and TP53 mutations (P = 0.021). PD-L1 CPS had no correlation with tumor mutational burden (Spearman's correlation coefficient 0.067). PD-L1 CPS was not significantly associated with hepatitis B virus infection. CONCLUSIONS: Our data indicated that patients with higher Edmondson-Steiner grade (grade III) had significantly higher PD-L1 CPS than patients with lower Edmondson-Steiner grade (grade II). Patients with TP53 mutations had significantly higher PD-L1 expression.

Effect of Postoperative Radiotherapy in Thymoma Patients: A SEER-Based Study.

INTRODUCTION: The role of postoperative radiation therapy (PORT) for thymoma is under debate, especially in patients aged ≥60 years with an advanced stage (Masaoka stages III and IV). We aimed to evaluate the efficacy of PORT for thymoma in a population-based registry. METHODS: A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to compare the outcomes of thymoma patients with or without PORT. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Conditional inference tree analyses were performed for risk classification according to the study variables. Cox regression was performed to evaluate the prognostic effect of PORT in the specific subgroups. RESULTS: A total of 2,236 patients were included. The conditional inference tree analysis identified that an age ≥60, a Masaoka stage ≥3, and the year of diagnosis were important factors when classifying patients into prognostic subgroups. PORT was found to be a protective predictor of OS in patients aged ≥60 years, those with a Masaoka stage III-IV, and those diagnosed after 2005. Further subgroup analyses revealed that PORT was significantly associated with a better OS (HR = 0.77) in patients aged ≥60 years, whereas it was not significantly associated with CSS. CONCLUSIONS: An older age (≥60 years) is critical for predicting survival outcomes in thymoma patients. Moreover, patients aged ≥60 years could benefit from PORT in terms of OS.

Temporal dynamics of Arc/Arg3.1 expression in the dorsal striatum during acquisition and consolidation of a motor skill in mice.

Region- and pathway-specific plasticity within striatal circuits is critically involved in the acquisition and long-term retention of a new motor skill as it becomes automatized. However, the molecular substrates contributing to this plasticity remain unclear. Here, we examined the expression of the activity-regulated cytoskeleton-associated protein (Arc) in the associative or dorsomedial striatum (DMS) and the sensorimotor or dorsolateral striatum (DLS), as well as in striatonigral and striatopallidal neurons, during different skill learning phases in the accelerating rotarod task. We found that Arc was mainly expressed in the DMS during early motor learning and progressively increased in the DLS during gradual motor skill consolidation. Moreover, Arc was preferentially expressed in striatopallidal neurons early in training and gradually increased in striatonigral neurons later in training. These data demonstrate that in the dorsal striatum, the expression of Arc exhibits a region- and cell-specific transfer during the learning of a motor skill, suggesting a link between striatal Arc expression and motor skill learning in mice.

Association between triglyceride glucose index and abnormal liver function in both urban and rural Chinese adult populations: Findings from two independent surveys.

The purpose of this study was to investigate the association between triglyceride glucose (TyG) index and abnormal liver function both in urban and rural Chinese adult populations. The 5824 urban (Nanjing) and 20,269 rural (Hefei) Chinese adults, from random selected households provided clinical history, glucose, lipids, anthropometric, and blood pressure measurements. Liver functions were assessed using Alanine Aminotransferase (ALT). Linear regression was applied to examine the dose-response relationship between TyG index and ALT. Logistic regression was used to estimate the association between TyG index and abnormal liver and function. Cubic spline models were applied to investigate the dose-response association between TyG index and abnormal liver function. C-statistics was used to compare the discriminable capacity over triglyceride, glucose and TyG index. Linear dose-response relationship was identified between TyG index and ALT as 1.222 IU increase by 1 unit increase of TyG index (1.242 for urban population and 1.210 for rural population). The 6.0% of urban and 11.0% of rural Chinese adults were observed to have abnormal liver function. The linear association between TyG index and abnormal liver function was revealed as 2.044 (1.930 to 2.165) of odds ratio by in unit increase of TyG index (2.334 for urban population and 1.990 for rural population). Higher C-statistics was found for TyG index compared with fasting glucose and triglyceride both in Chinese urban and rural populations. This study suggested in both urban and rural Chinese adult populations, TyG index is associated with abnormal liver function. TyG index is a potential indicator to identify high-risk individuals with metabolic disorders, for example impaired liver function in Chinese population, especially in Chinese urban population.

Successful response to the combination of immunotherapy and chemotherapy in cholangiocarcinoma with high tumour mutational burden and PD-L1 expression: a case report.

BACKGROUND: Cholangiocarcinoma, or bile duct cancer, is a gastrointestinal cancer with limited therapeutic options and a poor outcome. Studies have revealed that some major driver genes are associated with cholangiocarcinoma, but no targeted therapies have been approved. Immune checkpoint inhibitors, which are represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential therapy for multiple types of solid cancers. CASE PRESENTATION: A 53-year-old female presented with postoperative recurrence of PD-L1-positive intrahepatic cholangiocarcinoma with a high tumour mutational burden. This patient exhibited a marked response to the combination of anti-PD-1 immunotherapy and chemotherapy. CONCLUSIONS: As far as we know, this is the first case report on the success of the combination of immunotherapy and chemotherapy for advanced cholangiocarcinoma with PD-L1 positivity and a high tumour mutational burden.

[Functional plasticity of trigeminal motor nucleus in unilateral mastication model rats].

To observe the plasticity changes of trigeminal motor nucleus (Mo5) and masseter H-reflex in unilateral mastication model rats and explore the possible mechanism of functional plasticity in motor center involved in unilateral mastication, 54 adult male Wistar rats were randomly divided into 1-month (n = 10), 3-month (n = 10), and 16-month (n = 7) model groups and their corresponding control groups, respectively. Unilateral mastication model rats were prepared by intermittent removal of clinical crowns of left teeth (model side). Rats were anesthetized (20% urethane, i.p.), and bilateral Mo5 were chosen to conduct extracellular recordings, while bilateral electromyography (EMG) of masseter muscle and its H-reflex were simultaneously recorded by a polygraph. It was observed that the firing rate of Mo5 neurons in model sides was significantly lower than that of right sides in 3 model groups, and that of left sides in their control groups. The response latency of Mo5, which was evoked by electrical stimulation of masseter nerve in model sides of 1-month and 3-month model groups, was significantly longer than that of left sides in their control groups. Moreover, the amplitude of H-wave in model sides of 3-month and 16-month model groups was lower than that of left sides in their control groups when H-reflex was evoked by electrical stimulation of left masseter nerve. These results suggest that unilateral mastication in model rats decreases the Mo5 neuron excitability, and this may be one of the functional plasticity mechanisms in motor center involved in unilateral mastication.

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). METHODS: Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m(2) on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles). RESULTS: Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively. CONCLUSIONS: The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.

Predictive and prognostic value of ER-α36 expression in breast cancer patients treated with chemotherapy.

BACKGROUND: This study is to investigate the predictive and prognostic value of ER-α36 expression in breast cancer patients treated with chemotherapy. METHODS: ER-α36 expression in 120 breast cancer tumors was assessed by an immunohistochemistry assay. All patients were divided into two groups according to the chemotherapy procedure: group A, 50 patients who underwent neoadjuvant chemotherapy before surgery; group B, 70 patients who were performed adjuvant chemotherapy after surgery, and they all took at least two cycles of anthracycline-based and/or paclitaxel-based chemotherapy after surgery. The therapy effect on group A patients was evaluated two cycles later by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0). RESULTS: ER-α36 protein was positively expressed in 51 tumor specimens (42.5%) and no correlation was found between the expression of ER-α 36 and the expression of the full-length ER-α (ER-α66), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), Ki-67, tumor sizes, and the numbers of lymph node metastasis. Patients with ER-α36 negative expression tumors treated with the neoadjuvant chemotherapy had a higher remission rate [partial response: stable: progressed (n) 25:3:1 vs.11:9:1; P=0.009], a better response (86% vs. 52%; P=0.009), and a more favorable outcomes in triple-negative breast cancer patients compared to ER-α36 positive patients and ER-α36 negative expression was correlated with DFS in patients treated with neoadjuvant chemotherapy. CONCLUSIONS: ER-α36 negative tumors benefit more from neoadjuvant chemotherapy and have better prognosis, which may warrant further studies with larger size of the sample.

Analysis of urinary metabolites for breast cancer patients receiving chemotherapy by CE-MS coupled with on-line concentration.

OBJECTIVE: This study aimed to explore the relationship between urinary metabolites and clinical chemotherapy response in breast cancer by CE-MS coupled with on-line concentration. DESIGN AND METHODS: Urine samples were obtained from patients with advanced or locally advanced breast cancer (n=21) before and after chemotherapy and healthy volunteers (n=21). A rapid and sensitive hexadimethrine bromide-coating CE-MS method coupled with normal stacking is developed for the determination of organic acids in human urine. Another CE-MS method coupled with pH-mediated sample stacking is used for the analysis of amino acids and organic acids. RESULTS: After receiving chemotherapy, chemotherapy-sensitive patients showed 30% change in metabolite levels compared to healthy people, while chemotherapy-insensitive patients showed only 9% change in metabolite levels compared to healthy people showing recurrence. The extent of energy insufficiency for chemotherapy-insensitive patients was greater than that for chemotherapy-sensitive patients. CONCLUSIONS: Urinary metabolic products may be new potential predictive markers for therapy efficacy. However, more studies with a larger sample size are required to confirm these conclusions.

Carotenoid intake and esophageal cancer risk: a meta-analysis.

This meta-analysis was conducted to evaluate the association between intake of carotenoids and risk of esophageal cancer. A systematic search using PubMed, Cochrane Library, Web of Science, Scopus, CNKI, and CBM (updated to 6 May 2012) identified ten articles meeting the inclusion criteria with 1,958 cases of esophageal cancer and 4,529 controls. Higher intake of beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin reduced esophageal cancer risk with pooled ORs of 0.58 (95% CI 0.44, 0.77), 0.81 (95% CI 0.70, 0.94), 0.75 (95% CI 0.64, 0.86), 0.80 (95% CI 0.66, 0.97), and 0.71 (95% CI 0.59, 0.87), respectively. In subgroup analyses, beta-carotene showed protective effects against esophageal adenocarcinoma in studies located in Europe and North America. Alpha-carotene, lycopene, and beta-cryptoxanthin showed protection against esophageal squamous cell cancer. This meta-analysis suggested that higher intake of carotenoids (beta-carotene, alpha- carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin) is associated with lower risk of esophageal cancer. Further research with large-sample studies need to be conducted to better clarify the potentially protective mechanisms of carotenoid associations risk of different types of esophageal cancer.

Primary squamous cell carcinoma of the esophagus initially presenting as a large retroperitoneal mass: A case diagnosed as cancer of unknown primary site.

Retroperitoneal squamous cell carcinoma (SCC) of unknown origin is uncommon. It is extremely rare when the primary site detected in the esophagus after 18 months. A 59-year-old female patient with waist pain was initially diagnosed as retroperitoneal metastatic SCC of occult origin. Six cycles of chemotherapy with cisplatin, paclitaxel and 5-fluorouracil were administered and clinical complete response was observed. The primary site was detected in the esophagus after 18 months and the overall survival (OS) was 28 months. To the best of our knowledge, this is the first case of esophageal squamous cell carcinoma (ESCC) initially presenting as a metastatic site with long progression-free survival (PFS) and OS. In conclusion, the different biological characteristics and complete response to first-line chemotherapy likely contribute to relatively long PFS and OS.

[Analysis of serum metabonome of patients with breast cancer by gas chromatography-mass spectrometry].

OBJECTIVE: To analyze serum metabonome of patients with breast carcinoma by gas chromatography-mass spectrometry (GC-MS). METHODS: Serum samples from 30 patients with breast carcinoma and 25 normal people were collected. Endogenous metabolites amino acids, fatty acids, saccharides and organic acids were analyzed after derivatization. RESULT: The injection precision and intra-day precision (RSD) were less than 14.4 %. The method displayed good recovery (80.7 %-118.0 % with RSD<12.0 %) and linearity (r(2)>0.9905). Samples were stable in 24 h at room temperature. The samples were stable through three freeze-thaw cycles (RSD<14.6 %). Alaine,oxalate and glutamine were found with frequency of 96.7 %, 100 % and 93.3 %, respectively, which indicated that they may be the potential biomarkers. CONCLUSION: The method is stable and reliable, which may be helpful for the diagnosis of breast cancer as an auxiliary method.

A Phase II trial of oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX4) as first-line chemotherapy in advanced colorectal cancer: a China single-center experience.

PURPOSE: To evaluate the efficacy and toxicity of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every 2 weeks on previously untreated advanced colorectal cancer patients in Chinese population. PATIENTS AND METHODS: Forty-nine patients were enrolled to receive, entirely as inpatients, 2-weekly cycles of oxaliplatin 85 mg/m2 i.v. over 2 hours on Day 1, together with leucovorin 200 mg/m2 over 2 hours, 5-FU 400 mg/m2, bolus, followed by a 22-hours infusion of 5-FU at 600 mg/m2 Days 1-2 (FOLFOX4) every 2 weeks. Treatment was given until progression or unmanageable toxicity. In all, 49 patients received ≥ 1 oxaliplatin dose and a median of 7 treatment cycles (range 1∼27 cycles). RESULTS: Of the 45 eligible patients, 1 complete response (CR) and 18 partial responses (PRs) were observed for an overall response rate of 42.2 percent (95 percent confidence interval 26∼56 percent). Median progression-free survival was 7.2 months (6.4∼8.0) and median overall survival was 14.8 months (13.1∼16.5). Six patients (12.2 percent) reported Grade 3∼4 neutropenia. Thirty-one patients (62.3 percent) experienced Grade 1∼3 neurotoxicity and only 5 patients (10.2 percent) experienced Grade 3 neurotoxicity. CONCLUSION: In our experience, FOLFOX4 regimen is active and well tolerated in patients with previously untreated advanced colorectal cancer in Chinese population.