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Objective We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. Methods Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2 weeks of treatment. Results After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. Significance Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection.

Background Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. Materials and Methods The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation. Results Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. Conclusion Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. Implications for Practice Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.

Background/Aims: Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. Methods: The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays. The effects of RA190 on the proliferation and survival of both established ICC cell lines and primary ICC cells were examined in vitro. Annexin V/propidium iodide staining, western blotting and immunohistochemical staining were performed. The in vivo anti-tumor effect of RA190 on ICC was validated in subcutaneous xenograft and patient-derived xenograft (PDX) models. Results: ADRM1 levels were significantly higher in ICC tissues than in normal bile duct tissues. ICC patients with high ADRM1 levels had worse overall survival (hazard ratio [HR] = 2.383, 95% confidence interval [CI] =1.357 to 4.188) and recurrence-free survival (HR = 1.710, 95% CI =1.045 to 2.796). ADRM1 knockdown significantly inhibited ICC growth in vitro and in vivo. The specific inhibitor RA190 targeting ADRM1 suppressed proliferation and reduced cell vitality of ICC cell lines and primary ICC cells significantly in vitro. Furthermore, RA190 significantly inhibited the proteasome by inactivating ADRM1, and the consequent accumulation of ADRM1 substrates decreased the activating levels of NF-κB to aggravate cell apoptosis. The therapeutic benefits of RA190 treatment were further demonstrated in both subcutaneous implantation and PDX models. Conclusions: Our findings indicate that up-regulated ADRM1 was involved in ICC progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment.

Background Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. Methods Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. Results Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. Conclusions Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients. Electronic supplementary material The online version of this article (10.1186/s40425-019-0554-8) contains supplementary material, which is available to authorized users.

// Chu-Yu Jing 1, * , Yi-Peng Fu 1, * , Hu-Jia Shen 1, * , Su-Su Zheng 1 , Jia-Jia Lin 1 , Yong Yi 1 , Jin-Long Huang 1 , Xin Xu 1 , Juan Zhang 1 , Jian Zhou 1 , Jia Fan 1 , Zheng-Gang Ren 1 , Shuang-Jian Qiu 1 , Bo-Heng Zhang 1 1 The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P.R. China. * These authors have contributed equally to this work Correspondence to: Bo-Heng Zhang, email: zhang.boheng@zs-hospital.sh.cn Keywords: albumin, gamma-glutamyltransferase, intrahepatic cholangiocarcinoma, prognosis, nomogram Received: September 06, 2016 Accepted: December 27, 2016 Published: January 05, 2017 ABSTRACT The prognosis of intrahepatic cholangiocarcinoma (ICC) remains poor whereas predictive models for survival prediction in ICC patients following curative resection are limited. Herein, we established a novel inflammation-based score derived from preoperative albumin to gamma-glutamyltransferase ratio (AGR) and evaluated its prognostic significance in ICC patients underwent curative resection. Prognostic value of AGR was retrospectively studied in a cohort comprising 206 ICC patients following curative resection. The predictive performance of AGR was compared with other inflammation-based scores and serological tumor markers in terms of concordance index (C-index). Further, prognostic nomograms incorporating AGR into the tumor-node-metastasis (TNM) staging systems were established to achieve a better discriminatory ability. The optimal cut-off value of AGR was 0.6. Multivariate analysis showed that AGR was an independent predictor for overall survival (OS; P = 0.003) and recurrence-free survival (RFS; P = 0.046). The C-index of AGR was superior to other inflammation-based scores and serological tumor markers in OS and RFS prediction. The established nomograms showed improved predictive accuracy compared with the TNM staging systems alone. These results indicate that AGR is an independent prognostic indicator for ICC underwent curative resection. The incorporation of AGR into the existing TNM staging systems achieved improved predictive accuracy.

Previous research demonstrated that resveratrol possesses promising properties for preventing obesity. Endoplasmic reticulum (ER) stress was proposed to be involved in the pathophysiology of both obesity and hepatic steatosis. In the current study, we hypothesized that resveratrol could protect against high-fat diet (HFD)-induced hepatic steatosis and ER stress and regulate the expression of genes related to hepatic steatosis. Rats were fed either a control diet or a HFD for 12 weeks. After 4 weeks, HFD-fed rats were treated with either resveratrol or vehicle for 8 weeks. Body weight, serum metabolic parameters, hepatic histopathology, and hepatic ER stress markers were evaluated. Moreover, an RT2 Profiler Fatty Liver PCR Array was performed to investigate the mRNA expressions of 84 genes related to hepatic steatosis. Our work showed that resveratrol prevented dyslipidemia and hepatic steatosis induced by HFD. Resveratrol significantly decreased activating transcription factor 4, C/EBP-homologous protein and immunoglobulin binding protein levels, which were elevated by the HFD. Resveratrol also decreased PKR-like ER kinase phosphorylation, although it was not affected by the HFD. Furthermore, resveratrol increased the expression of peroxisome proliferator-activated receptor δ, while decreasing the expression of ATP citrate lyase, suppressor of cytokine signaling-3, and interleukin-1β. Our data suggest that resveratrol can prevent hepatic ER stress and regulate the expression of peroxisome proliferator-activated receptor δ, ATP citrate lyase, suppressor of cytokine signaling-3, tumor necrosis factor α, and interleukin-1β in diet-induced obese rats, and these effects likely contribute to resveratrol's protective function against excessive accumulation of fat in the liver.

Objective To observe the therapeutic effect of acupuncture plus psychological intervention for postpartum depression.

Objective To observe the effect of electroacupuncture (EA) combined with Stretta radiofrequency treatment on contents of motilin (MTL) and gastrin (GAS) in gastroesophageal reflux disease (GERD) patients.

Objective To observe the effect of combining spreading moxibustion and point injection on serum eosinophil cationic protein (ECP), lipid peroxidase (LPO) and cellular immunity in patients with cough-variant asthma.

Objective To observe the clinical effect on cervical spondylosis of nerve root type treated by warm needling therapy at Jiaj ( EX-B 2) and plum-blossom needle therapy. Methods According to the random number table, 150 cases of cervical spondylosis of nerve root type were randomized into an acupuncture-moxibustion group (75 cases) and a control group (75 cases). In the acupuncture-moxibustion group, the warm needling at EX-B 2 and tapping with plum-blossom needle were applied. EX-B 2 on the affected segments were selected and stimulated with warm needling technique for 20–30 min. Afterward, the plum-blossom needle was used to tap the skin around the acupoints, for 3 min on each site. The treatment was given once every day. Seven treatments made one session. The interval between two sessions was 1 day. In the control group, the medication was used in combination with traction therapy. The intravenous drip with 5% glucose 250 mL and compound salvia miltiorrhiza injection 40 mL was used, once a day. In traction treatment, the patient was in a sitting position, neck anteflexion at 15°-30°, traction force at 10%–20% of the body mass, for 20–30 min in each time. The treatment was given once every day. The appointed person evaluated therapeutic effects after the three sessions of treatment in the two groups. Results The clinical curative rate was 49.3% (37/75) and the total effective rate was 94.7% (71/75) in the acupuncture-moxibustion group and those were 24.0% (18/75) and 81.3% (61/75) respectively in the control group. The total effective rate and clinical curative rate in the acupuncture-moxibustion group were superior to the control group (both P Conclusion The warm needling therapy at EX-B 2 and tapping therapy with plum-blossom needle achieve the significant effect on cervical spondylosis of nerve root type.

OBJECTIVE γ-Glutamyltransferase (GGT) has been used as a diagnostic biomarker for hepatobiliary disease. However, little is known about its role in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to validate the clinical significance of GGT in predicting the prognosis of ICC patients. MATERIALS AND METHODS A total of 411 patients with pathologically confirmed ICC were retrospectively analyzed. Of them, 307 patients underwent hepatectomy, 64 patients with unresectable tumors were treated with chemotherapy (n=42) or transcatheter arterial chemoembolization (n=22), and 40 patients with end-stage disease received supportive treatment. The association between GGT and the clinicopathological features and prognosis was assessed. RESULTS Serum GGT levels were significantly associated with hepatitis B infection (P=0.02), the Child-Pugh grade (P=0.02), vascular invasion (P

Objective To observe the effect of stage-based acupuncture on neuron specific enolase (NSE), homocysteine (Hcy) levels and magnetic resonance spectrum in patients with cerebral infarction.

Eight novel 1,4-disubstituted phthalazines ( 7 – 14 ) were designed and synthesized. The structures of all the synthesized compounds were confirmed by IR, 1 H NMR, 13 C NMR, MS and elemental analysis. Their in vitro cytotoxicity against cancer cell lines (Bel-7402 and HT-1080) were evaluated by standard MTT assay. Among them, compounds 9 and 11 exhibited more potent cytotoxicity than cisplatin.

Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, its accuracy in hepatocellular carcinoma (HCC) patients is unknown. The aim of this study was to investigate the prognostic significance of PCT in patients with unresectable HCC treated with transcatheter arterial chemoembolization (TACE). A total of 509 patients with unresectable HCC initially treated with TACE were enrolled in this retrospective study. According to quartile of the PCT values, all patients were divided into 4 groups. Overall survival (OS) was evaluated with the Kaplan–Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for evaluating the significance of the prognostic factor. The median follow-up period was 18 months and there were significant differences in the survival rates between the 4 groups. The HR (95% CI) for all-cause mortality comparing patients with PCT Quartile2–4 to patient with Quartile1 (HR = 1.00) were 1.353 (1.023–1.791), 1.799 (1.354–2.390), 1.960 (1.455–2.639), respectively, (P

Supplemental Digital Content is available in the text, Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection. A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria. Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775–0.799) and 0.714 (95%CI 0.695–0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA. The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection.

Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

This study evaluated the effects Governor Vessel electroacupuncture (GVEA) on the systematic regulation of neurotrophic factors (NTFs) in the spinal segments caudal (CSS) to the site of transection in rats subjected to spinal cord transection (SCT). Using RT-PCR, we amazingly found the gene expressions of NGF, IGF-1, FGF-2, CNTF, PDGF, TGF-β1, TrkA, TrkB and TrkC were downregulated following GVEA treatment. However, the number of GAP-43 and Synaptophysin profiles in the CSS in the GVEA rats showed a significant increase, compared with non-EA animals, although both the 5-HT and corticospinal fibers have no statistical differences in the CSS. Simultaneously, there was significant recovery in hindlimb locomotor and sensory functions after GVEA treatment. Therefore, these findings challenge the past view that GVEA promotes functional restoration, which is linking to the up-regulation of NTFs in rats subjected to SCT. The present findings may give some novel indication on the mechanism of acupuncture for the treatment of SCI.