Effectiveness of acupuncture for postoperative gastrointestinal recovery in patients undergoing thoracoscopic surgery: a prospective randomized controlled study.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications among patients who have undergone thoracic surgery. Acupuncture has long been used in traditional Chinese medicine to treat gastrointestinal diseases and has shown benefit as an alternative therapy for the management of digestive ailments. This study aimed to explore the therapeutic effectiveness of acupuncture as a means to aid postoperative recovery of gastrointestinal function in patients undergoing thoracoscopic surgery. METHODS: In total, 112 patients aged 18-70 years undergoing thoracoscopic surgery between 15 June 2022 and 30 August 2022 were randomized into two groups. Patients in the acupuncture group (AG) first received acupuncture treatment 4 h after surgery, and treatment was repeated at 24 and 48 h. Patients in the control group (CG) did not receive any acupuncture treatment. Both groups received the same anesthetic protocol. Ultrasound-guided thoracic paravertebral block (TPVB) was performed in the paravertebral spaces between T4 and T5 with administration of 20 mL of 0.33% ropivacaine. All patients received patient-controlled intravenous analgesia (PCIA) after surgery. RESULTS: Median time to first flatus [interquartile range] in the AG was significantly less than in the CG (23.25 [18.13, 29.75] vs 30.75 [24.13, 45.38] h, p < 0.001). Time to first fluid intake after surgery was significantly less in the AG, as compared with the CG (4 [3, 7] vs 6.5 [4.13, 10.75] h, p = 0.003). Static pain, measured by visual analog scale (VAS) score, was significantly different on the third day after surgery (p = 0.018). Dynamic pain VAS scores were lower in the AG versus CG on the first three postoperative days (p = 0.014, 0.003 and 0.041, respectively). CONCLUSION: Addition of acupuncture appeared to improve recovery of postoperative gastrointestinal function and alleviate posteoperative pain in patients undergoing thoracoscopic surgery. Acupuncture may represent a feasible strategy for the prevention of PGD occurrence. TRIAL REGISTRATION NUMBER: ChiCTR2200060888 (Chinese Clinical Trial Registry).

Breast cancer-related lymphedema and recurrence of breast cancer: Protocol for a prospective cohort study in China.

INTRODUCTION: The primary aim is to determine the factors associated with breast cancer-related lymphedema and to identify new associated factors for the recurrence of breast cancer and depression. The secondary objective is to investigate the incidence of breast cancer-related events (breast cancer-related lymphedema, recurrence of breast cancer, and depression). Finally, we want to explore and validate the complex relationship among multiple factors influencing breast cancer complications and breast cancer recurrence. PATIENTS AND METHODS: A cohort study of females with unilateral breast cancer will be conducted in West China Hospital between February 2023 and February 2026. Breast cancer survivors in the age range of 17-55 will be recruited before breast cancer surgery. We will recruit 1557 preoperative patients with a first invasive breast cancer diagnosis. Consenting breast cancer survivors will complete demographic information, clinicopathological factors, surgery information, baseline information, and a baseline depression questionnaire. Data will be collected at four stages: the perioperative stage, chemotherapy therapy stage, radiation therapy stage, and follow-up stage. Data including the incidence and correlation of breast cancer-related lymphedema, breast cancer recurrence, depression, and medical cost will be collected and computed through the four stages above. For every statistical analysis, the participants will be classified into two groups based on whether they develop secondary lymphedema. Incidence rates of breast cancer recurrence and depression will be calculated separately for groups. Multivariate logistic regression will be used to determine whether secondary lymphedema and other parameters can predict breast cancer recurrence. DISCUSSION: Our prospective cohort study will contribute to establishing an early detection program for breast cancer-related lymphedema and recurrence of breast cancer, which are both associated with poor quality of life and reduced life expectancy. Our study can also provide new insights into the physical, economic, treatment-related and mental burdens of breast cancer survivors.

Mental health status of medical students during postgraduate entrance examination.

BACKGROUND: The postgraduate entrance examination can be a milestone for many medical students to advance their careers. An increasing number of students are competing for limited postgraduate offers available, and failure to enter postgraduate studies can have adverse mental health consequences. In this paper, we aim to investigate the mental health status of medical students during the postgraduate application entrance examination and to provide a targeted basis for mental health education and psychological counselling. METHODS: Using the Symptom Checklist-90 scale (SCL-90) questionnaire, the mental health status of 613 students who passed two rounds of the Postgraduate Entrance Examination in 2019 to enroll in Guangzhou Medical University in China was evaluated and followed up for retesting 6 months later. We used SPSS 20.0 statistical software for comparative analysis, including One-Sample T-Test, Independent-Samples T-Test, Paired Samples T-Test and Chi-square Test. RESULTS: Our data showed that 12.10% of students had mental health problems during the postgraduate entrance examination, and it decreased significantly to 4.40% at the 6-month follow-up after the examination period finished (P < 0.01). Somatization was the most significant symptom of the students both during and after the postgraduate entrance examination stages. All SCL-90 factors were scored significantly lower both in and after the postgraduate entrance examination stages than the 2008 national college student norm score (P < 0.01). Excluding psychiatric factors, all other SCL-90 factors in the postgraduate entrance examination stage scored higher than the graduate stage (P < 0.05), and the total score of SCL-90 in female medical students was higher compared to male students (P < 0.05). CONCLUSION: The postgraduate entrance examination event has a significant negative influence on students' mental health. The mental health of college and graduate students as an important part of their higher education experience should be systematically studied, and psychological counselling or help should be provided to them throughout their studies, specifically during the examination period. Educating applicants about mental health should be implemented during the postgraduate entrance examination curriculum.

Household Wealth and Individuals' Mental Health: Evidence from the 2012-2018 China Family Panel Survey.

Based on the data from the 2012-2018 China Family Panel Survey, this study examines the impact of household wealth on individuals' mental health using a two-way fixed effects model. The findings indicate that household wealth exerts a significant positive effect on individuals' mental health. Furthermore, this study shows that the impact of household wealth on individuals' mental health is nonlinear but inverted U-shaped. Considering the possible endogeneity problem, this study further examines the effect of household wealth on residents' mental health using two-stage least squares, and the conclusions remain robust. The results of the heterogeneity analysis indicate that household wealth has a greater impact on the mental health of residents in the low-education group and western region. Furthermore, the results of the mechanisms reveal that household wealth affects mental health by influencing insurance investment and individuals' labor supply. Moreover, this study finds that household wealth affects individuals' mental health not only in the short term but also in the medium and long terms. This study provides policy implications for the government toward improving individuals' mental health.

Bioelectrical impedance analysis for early screening of upper limb subclinical lymphedema: A case-control study.

Breast cancer-related lymphedema is a treatment-related chronic disease that causes great distress and medical burden. Early screening and precautionary measures for lymphedema could improve well-being and decrease medical costs. Herein, we used bioelectrical impedance analysis for early screening of lymphedema. We set up a verifiable standardized subclinical standard to screen subclinical lymphedema in postoperative breast cancer patients using bioelectrical impedance. The first part determined the criteria of subclinical lymphedema. Among the 424 female participants, 127 were healthy women, whereas 297 were postoperative breast cancer survivors. Subclinical standard boundaries were determined by the 95% confidence interval of the healthy women. The screening rate of patients with subclinical lymphedema was inferred by comparing the subclinical standard boundaries and the postoperative patient values. A total of 14.81-20.87% of postoperative breast cancer survivors were identified as patients with subclinical lymphedema. The second part provided the results of the verification test of this subclinical standard. The data of the verification test from 30 healthy women and 30 screened patients met the subclinical standard, and 30 breast cancer survivors with lymphedema verified the utility and feasibility of the subclinical standard. Therefore, this standard could provide a screening tool for early the identification of subclinical breast cancer survivors. Early detection helps implement personal and precise medical precautions for patients with subclinical lymphedema.

Systematic evaluation of line probe assays for the diagnosis of tuberculosis and drug-resistant tuberculosis.

BACKGROUND: Line probe assays (LPAs) are PCR-based assays used for the rapid diagnosis of Mycobacterium tuberculosis (MTB) and drug-resistant tuberculosis (DR-TB). But studies on its performance are insufficient. Thus, in this study, we conducted a systematic review and meta-analysis to evaluate the effect of LPAs in the detection of MTB and drug-resistant TB in comparison with the traditional culture and DST methods. METHODS: A systemic literature search was conducted on the Web of Science, Embase, PubMed, the Cochrane Library, Scopus, and OVID databases. All the included studies were classified according to different detecting objects. Sensitivity, specificity, Positive Likely Ratio (PLR), Negative Likely Ratio (NLR), Diagnostic Odds Ratio (DOR), corresponding 95% confidence interval, Area Under Curve (AUC), Deeks' funnel plot, and Bivariate Boxplot was used to do the evaluation. RESULTS: 147 studies included 491 datasets, with 182,448 samples, were incorporated into our analysis. The sensitivity (95% CI), specificity (95% CI), PLR, NLR, DOR and AUC for MTB were 0.89 (0.86 to 0.92), 0.94 (0.90 to 0.97), 15.70, 0.11, 139 and 0.96, respectively; for rifampicin-resistant TB were 0.96 (0.95 to 0.97), 0.99 (0.98 to 0.99), 82.9, 0.04, 1994 and 1.00, respectively; for isoniazid-resistant TB were 0.91 (0.89 to 0.93), 0.99 (0.98 to 0.99), 83.4, 0.09, (0.99 to 1.00), 195.7, 0.07, 2783 and 1.00, respectively; for Multi-drug resistant TB (MDR-TB) were 0.93 (0.90 to 0.95), 1.00 (0.99 to 1.00), 195.7, 0.07, 2783 and 1.00, respectively; for extensively drug-resistant TB (XDR-TB) were 0.60 (0.33 to 0.82), 1.00 (0.95 to 1.00), 291.3, 0.4, 726 and 0.95, respectively; for (second-line drug-resistant TB) SLID-TB were 0.83 (0.78 to 0.87), 0.98 (0.97 to 0.99), 44.6, 0.17, 262 and 0.98, respectively. Sensitivity in pre-extensively drug-resistant TB (Pre-XDR-TB) was 0.67, specificity was 0.91. No publication bias existed according to Deeks' funnel plot. CONCLUSION: High diagnosis performance was confirmed in LPAs for the diagnosis of MTB and drug-resistant TB. LPAs might be a good alternative to culture and DST in detecting MTB, RR-TB, INH-TB, XDR-TB, SLID-TB, and MDR-TB. While more studies were still needed to explore the diagnosis performance of LPAs for Pre-XDR TB.

Anesthetic propofol enhances cisplatin-sensitivity of non-small cell lung cancer cells through N6-methyladenosine-dependently regulating the miR-486-5p/RAP1-NF-κB axis.

BACKGROUND: Drug resistance is a considerable challenge for chemotherapy in non-small cell lung cancer (NSCLC). Propofol, a commonly used intravenous anesthetics, has been reported to suppress the malignancy of various cancers. However, the effects of propofol on cisplatin (DDP) sensitivity in NSCLC and its molecular mechanisms have not been clearly clarified yet, and the present study aimed to resolve this problem. METHODS: NSCLC cells were co-treated with propofol and DDP, Cell Counting kit-8 assay, colony formation assay and flow cytometry were conducted to test the role of propofol in regulating DDP-resistance in NSCLC. Next, through conducting quantitative real-time polymerase chain reaction, dual-luciferase gene reporter system and western blot, the responsible molecular axis in propofol regulating the DDP sensitivity in NSCLC was uncovered, and the function verification experiments were performed by transfection with the inhibitors or small interfering RNAs of those molecules. RESULTS: Propofol suppressed cell viability, colony formation ability, tumorigenesis, and promoted cell apoptosis to enhance DDP-sensitivity in NSCLC in vitro and in vivo. Propofol increased miR-486-5p level in NSCLC cells and xenograft tumors tissues in a N6-methyladenosine (m6A)-dependent manner, thus inactivating the Ras-associated protein1 (RAP1)-NF-kappaB (NF-κB) axis. Propofol regulated the miR-486-5p/RAP1-NF-κB axis to improve DDP-sensitivity in NSCLC. CONCLUSIONS: Taken together, this study firstly investigates the detailed molecular mechanisms by which propofol enhanced DDP-sensitivity in NSCLC cells, and a novel m6A-dependent miR-486-5p/RAP1-NF-κB axis is identified to be closely associated with the process.

Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats.

Background: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. Objectives: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. Methods: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 µg), neostigmine (0.3, 1, 3, and 10 µg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. Results: Intrathecally administered pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. Conclusions: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.

Verte-Box: A Novel Convolutional Neural Network for Fully Automatic Segmentation of Vertebrae in CT Image.

Due to the complex shape of the vertebrae and the background containing a lot of interference information, it is difficult to accurately segment the vertebrae from the computed tomography (CT) volume by manual segmentation. This paper proposes a convolutional neural network for vertebrae segmentation, named Verte-Box. Firstly, in order to enhance feature representation and suppress interference information, this paper places a robust attention mechanism on the central processing unit, including a channel attention module and a dual attention module. The channel attention module is used to explore and emphasize the interdependence between channel graphs of low-level features. The dual attention module is used to enhance features along the location and channel dimensions. Secondly, we design a multi-scale convolution block to the network, which can make full use of different combinations of receptive field sizes and significantly improve the network's perception of the shape and size of the vertebrae. In addition, we connect the rough segmentation prediction maps generated by each feature in the feature box to generate the final fine prediction result. Therefore, the deep supervision network can effectively capture vertebrae information. We evaluated our method on the publicly available dataset of the CSI 2014 Vertebral Segmentation Challenge and achieved a mean Dice similarity coefficient of 92.18 ± 0.45%, an intersection over union of 87.29 ± 0.58%, and a 95% Hausdorff distance of 7.7107 ± 0.5958, outperforming other algorithms.

Fast Segmentation of Vertebrae CT Image Based on the SNIC Algorithm.

Automatic image segmentation plays an important role in the fields of medical image processing so that these fields constantly put forward higher requirements for the accuracy and speed of segmentation. In order to improve the speed and performance of the segmentation algorithm of medical images, we propose a medical image segmentation algorithm based on simple non-iterative clustering (SNIC). Firstly, obtain the feature map of the image by extracting the texture information of it with feature extraction algorithm; Secondly, reduce the image to a quarter of the original image size by downscaling; Then, the SNIC super-pixel algorithm with texture information and adaptive parameters which used to segment the downscaling image to obtain the superpixel mark map; Finally, restore the superpixel labeled image to the original size through the idea of the nearest neighbor algorithm. Experimental results show that the algorithm uses an improved superpixel segmentation method on downscaling images, which can increase the segmentation speed when segmenting medical images, while ensuring excellent segmentation accuracy.

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN. METHODS: Systematic literature searches of PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Conventional meta-analysis with a random-effects model and trial sequential analysis (TSA) were performed. RESULTS: A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥ 2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥ 2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥ 2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, despite that GM1 was associated with a reduced risk of CTCAE grade ≥ 2 CIPN in the taxane subgroup of one study (OR 0.003, 95% CI 0.00-0.05). These results were confirmed by the sub-analysis of randomized controlled trials (RCTs). In TSA, the z-curve for the taxane subgroup crossed the upper trial sequential monitoring boundary (TSMB) but do not reach the required information size (RIS). The z-curves for the oxaliplatin subgroup remained in the nonsignificant area and did not reach the RIS. Further, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥ 2 adverse events such as fatigue, nausea, diarrhea, and rash. CONCLUSIONS: GM1 seemed to be well-tolerated and did not influence the anti-cancer effects of chemotherapeutic agents. Although the data did not confirm the effectiveness of GM1 in preventing oxaliplatin-induced peripheral neuropathy, GM1 might be able to prevent taxane-induced peripheral neuropathy. More studies are required in different ethnic populations receiving taxane-based chemotherapy to confirm these findings.

Preparation and conformational analysis of polyproline tri-helix macrocycle nanoscaffolds of varied sizes.

Ligand patterns at the nanoscale are essential in modulating biological recognition and signaling through binding to receptor oligomers. Biocompatible nanoscaffolds that allow precise control of multiple ligand presentation would be of great use in manipulating cellular processes and understanding membrane receptor biology. We have previously developed tri-helix and tetra-helix macrocycle scaffolds based on the Pro9 peptide helix to control ligand arrangements that can selectively target receptor oligomers. A better understanding of the structure of these macromolecules would significantly reduce the difficulty in designing matching ligand positions for target receptors. In this work, we expand the arsenal of ligand patterns by preparing polyproline tri-helix macrocycle scaffolds of different sizes. These synthetic nanoscaffolds composed of peptide helices ranging from Pro6 to Pro12 also allowed us to systematically investigate their properties. With a combination of circular dichroism spectroscopy and ion mobility spectrometry-mass spectrometry (IMS-MS), the measurement for varied sizes of these scaffolds indicated the connecting dihedral angle between both ends of the helix affects the strain in the cyclic scaffold. The experimental collision cross section obtained from IMS-MS favors a propeller model for the helix arrangements. The results not only contribute conformational insights for the polyproline tri-helix system, but also provide precious information for the future design and synthesis of cyclic nanostructures based on peptide helices.

Dynamic light scattering and fluorescence dual-signal sensing of cancer antigen-125 via recognition of the polymerase chain reaction product with gold nanoparticle probe.

Cancer antigen 125 (CA - 125) is an important biomarker for the diagnosis of ovarian cancer. In this paper, oligonucleotide 5'-GACAGGCCCGAAGGAATAGATAATACGACTCACTATAGGGAGACAAGAATAAACGCTCAA-3' (oligo 1) contains an aptamer of CA - 125, and was designed partly complementary to oligonucleotide 5'-CTCTCTCTCCACCTTCTTCTTTGAGCGTTTATTCTTGTCT-3' (oligo 2). Oligo 1 · oligo 2 was extended with the Klenow fragment (exo-) polymerase for further polymerase chain reaction (PCR) processes in the presence of two primers: deoxyribose nucleoside triphosphate and Taq polymerase. Single-stranded DNA was produced at two sides of the PCR product by introducing a C18 spacer into the two primers, which could hybridize with AuNPs-DNA probes, investigated by dynamic light scattering and fluorescence. The addition of CA - 125 can interrupt the hybridization between oligo 1 and oligo 2, causing the average diameter of AuNPs-DNA probes to decrease with the increase of CA-125 within the range of 5 fg mL-1 - 50 ng mL-1. The linear regression equation of this relationship was D = 430.48-49.60 log10C, with a detection limit of 1.1 fg mL-1. Fluorescein molecules were modified at the end of the forward primer. The fluorescence intensity of the PCR product can be measured simultaneously, with the fluorescence intensity increasing linearly with the logarithm of CA-125 concentration within a linear range from 10 fg mL-1 to 50 ng mL-1, with a detection limit of 1.5 fg mL-1.

Nomograms to predict survival outcomes after microwave ablation in elderly patients (>65 years old) with early-stage hepatocellular carcinoma.

Objectives: To develop and validate the nomograms to predict survival outcomes after microwave ablation (MWA) in elderly patients(>65 years old) with early-stage hepatocellular carcinoma (EHCC).Methods: This retrospective study was approved by the institutional review board. A total of 265 EHCC patients (76 females, 189 males; average age 71.4 years ± 5.4 [standard deviation]) with 345 nodules subsequently underwent MWA from April 2006 to October 2019. Baseline characteristics were collected to identify the risk factors for the determination of survival outcomes after MWA. The nomograms were based on prognostic factors for overall survival (OS) and recurrence-free survival (RFS) from the multivariate Cox proportional hazards model and validated in external cohorts from another two institutions (n = 130). The nomograms were assessed for their predictive accuracy using Harrell's concordance index (C-index).Results: After a median follow-up time of 28.6 months, 29.8% (79/265) of the patients died, and 54.3% (144/265) of the patients experienced recurrence in the training set. The OS nomogram was developed based on the hepatitis B virus (HBV) presence, α-fetoprotein (AFP), and albumin, with a C-index of 0.757 (95% confidence interval [CI]: 0.645, 0.789).The scores of the nomogram ranged from 0 to 24. The RFS nomogram was developed based on tumor number, abutting major vessels and platelets, with a C-index of 0.733 (CI: 0.672, 0.774). The likelihood of 3- and 5-year OS and RFS were consistent between clinical observations and nomogram predictions in external cohorts.Conclusions: The nomogram models can be useful in determining the risk of OS and RFS in elderly patients with EHCC after MWA, which can guide individual patient management.Key pointsMWA is an effective and feasible treatment for elderly patients with EHCC and can improve survival outcomes.A calibrated and objective nomogram model for the prediction of survival outcomes in elderly patients (>65 years old) may guide patient selection and MWA treatment.Older age was not deemed to be a risk factor for survival outcomes when the elderly patients with EHCC underwent MWA.

JTC-801 alleviates mechanical allodynia in paclitaxel-induced neuropathic pain through the PI3K/Akt pathway.

Chemotherapy-induced peripheral neuropathy is a serious adverse effect of chemotherapeutic agents such as paclitaxel. JTC-801, a nociceptin/orphanin FQ opioid peptide (NOP) receptor antagonist, has been reported to attenuate neuropathic pain in several pain models. However, the therapeutic significance and function of JTC-801 in chemotherapy-induced peripheral neuropathy remain unclear. In this study, we determined the effect of JTC-801 on neuropathic pain induced by paclitaxel, and we explored the potential mechanism in the dorsal root ganglion (DRG). The behavioral test showed that single or multiple systemic administrations of JTC-801 significantly alleviated mechanical allodynia in paclitaxel-treated rats. Using Western blot analysis and immunohistochemistry, we found that paclitaxel increased the expression of phosphatidylinositol 3-kinase (PI3K) and phospho-Akt (p-Akt) in the DRG. Double immunofluorescence staining indicated that p-Akt was expressed in neurons in the DRG. Multiple injections of JTC-801 significantly inhibited the activation of Akt and decreased the expression of inflammatory cytokines. The data suggest that JTC-801 alleviates mechanical allodynia associated with paclitaxel-induced neuropathic pain via the PI3K/Akt pathway.

Prognostic significance of neutrophil-to-lymphocyte ratio in middle thoracic esophageal squamous cell carcinoma patients undergoing radical esophagectomy.

BACKGROUND: It is widely accepted that the pretreatment neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of prognosis in multiple malignancies, including esophageal squamous cell carcinoma (ESCC). However, its predictive value in middle thoracic esophageal carcinoma is still unclear. Therefore, the purpose of this study was to investigate the preoperative serum levels of NLR in middle thoracic esophageal carcinoma patients to clarify their clinical significance as predictors of prognosis. METHODS: This study investigated 556 patients with middle thoracic ESCC treated by esophagectomy from January 2010 to December 2012. The prognostic impact of serum NLR level was analyzed. A receiver operating characteristic (ROC) curve was used to identify the NLR for predicting survival. Correlation between the NLR and clinicopathological characteristics was analyzed by χ2 test. Prognostic influence was calculated by using the Kaplan-Meier method and the difference was compared by log-rank test. Cox regression analysis was performed to evaluate the significant prognostic factors. RESULTS: The cutoff value for the NLR was 2.43 ng/mL, the area under the curve was 0.553 (95% CI: 0.504-0.601; P=0.035), and the sensitivity and specificity were 53.3% and 58.7% respectively. It is demonstrated that preoperative NLR (P=0.003), T stage (P<0.001), N stage (P<0.001), surgical approach (P=0.004), and gender (P=0.008) were independent prognostic factors in middle thoracic ESCC by univariate analysis. Multivariate analysis showed that preoperative NLR (P=0.036), T stage (P=0.004), N stage (P<0.001), surgical approach (P=0.002), and age (P=0.019) were independent prognostic factors for survival. CONCLUSIONS: Pretreatment NLR >2.43 ng/mL could serve as an indicator of poor prognosis in middle thoracic ESCC patients after surgical treatment.

Computed tomography-guided radiofrequency ablation of the retained iodized oil after simultaneous combination with transarterial embolization in small recurrent or residual hepatocellular carcinoma.

OBJECTIVE: To assess the clinical efficacy and safety of transarterial embolization (TAE) in simultaneous combination with computed tomography (CT)-guided radiofrequency ablation (RFA) for recurrent or residual hepatocellular carcinoma (HCC), and to determine the risk factors influencing local tumor progression following this procedure. METHODS: One hundred eighteen patients with recurrent or residual HCC (tumor size, 10-30 â€‹mm) underwent RFA. During the 19-month follow-up, 59 patients received RFA only (RFA group), and the remaining 59 received RFA immediately after TAE (TAE â€‹+ â€‹RFA group). All patients were followed up to observe the short-term therapeutic effects and complications. The cumulative local tumor progression rates in both groups were calculated using unpaired Student's t tests and the Kaplan-Meier method. RESULTS: The rate of major complications was 5.08% in the TAE â€‹+ â€‹RFA group and 3.39% in the RFA group. The overall response rate was 96.61% in the TAE â€‹+ â€‹RFA group and 79.66% in the RFA group (P â€‹= â€‹0.008). The disease control rate was significantly higher in the TAE â€‹+ â€‹RFA group than in the RFA group (94.92% vs. 79.66%, P â€‹= â€‹0.024). The median time to local tumor progression was 4.8 months in the RFA group and 9.6 months in the TAE â€‹+ â€‹RFA group. The cumulative local tumor progression rate at 1 year was 10.60% in the RFA group and 23.60% in the TAE â€‹+ â€‹RFA group (P â€‹= â€‹0.016). CONCLUSION: TAE in simultaneous combination with CT-guided RFA was effective and safe against recurrent or residual HCC. Local tumor progression can be minimized by the complete ablation of targeted iodized oil deposits after simultaneous TAE.

Which induction chemotherapy regimen followed by cisplatin-based concurrent chemoradiotherapy is the best choice among PF, TP and TPF for locoregionally advanced nasopharyngeal carcinoma?

BACKGROUND: Which induction chemotherapy (IC) regimen followed by cisplatin-based concurrent chemoradiotherapy (CCRT) is the best choice among PF (cisplatin and 5-fluorouracil), TP (docetaxel and cisplatin) and TPF (docetaxel, cisplatin, and 5-fluorouracil) remains controversial in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This Bayesian network meta-analysis investigated the efficacy and toxicity of these three common IC regimens and attempted to find the optimal chemotherapy regimen. METHODS: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) up to December, 2017. Then, we screened studies for eligibility, extracted data, assessed their quality, tested consistency, and used Bayesian network meta-analysis to combine direct and indirect evidence. RESULTS: Ten records were identified involving 7 eligible RCTs with 1,570 patients. Results of the Bayesian network meta-analysis shows that TPF [hazard ratios (HRs) 0.68; 95% credibility interval (CrI), 0.42-1.1], TP (HRs 0.70; 95% CrI, 0.22-2.2) and PF (HRs 1.0; 95% CrI, 0.71-1.5) have the probability of 49.61%, 47.45% and 1.57% respectively to be the optimal induction regimen. Docetaxel-based regimens, including TP [risk ratios (RRs) 5.9; 95% CrI, 1.4-26.0) and TPF (RRs 4.5; 95% CrI, 1.1-18.0), significantly increase the incidence of hematological toxicity. As for ≥ grade 3 mucositis, 5-fluorouracil-based regimens, including PF (RRs 2.1; 95% CrI, 0.91-5.8) and TPF (RRs 1.4; 95% CrI, 0.48-4. 6), are higher than TP (RRs 1.1; 95% CrI, 0.30-4.6). CONCLUSIONS: Only considering overall survival (OS), TPF has the highest probability to be the optimal choice in LA-NPC and TP also shows encouraging anti-tumor effects. However, we also noticed that TPF induced worse adverse events, especially in ≥ grade 3 hematological toxicity and oral mucositis.

AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2 pathway and downregulating IL-4.

Antitubulin chemotherapeutics agents, such as paclitaxel, are effective chemotherapy drugs for cancer treatment. However, painful neuropathy is a major adverse effect limiting the wider application of chemotherapeutics. In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity, resulted in reduced protein expression of nuclear factor of activated T cells 2 (NFAT2) in cell nuclei. Chromatin immunoprecipitation showed that, NFAT2 binds to the IL-4 gene promoter regulating the protein expression of IL-4. Overexpression of NFAT2 by intrathecal injection of the AAV5-NFAT2-GFP virus alleviated the pain behavior induced by paclitaxel via increasing the expression of IL-4. Knocked down AKAP150 by siRNA or AAV5-Cre-GFP partly restored the expression of IL-4 in DRG. Our results indicated that regulation of IL-4 via the CN/NFAT2 pathway mediated by AKAP150 could be a pivotal treatment target for paclitaxel-induced neuropathic pain and or other neuropsychiatric disorders.

Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer.

The prognosis of metastatic breast cancer is always very poor. Thus, it is urgent to develop novel drugs with less toxicity against metastatic breast cancer. A new drug (XC-591) derived from benzothiazole-2-thiol was designed and synthesized in our lab. In this study, we tried to assess effects of XC-591 treatment on primary breast cancer and pulmonary metastasis in 4T1 mice model. Furthermore, we tried to discover its possible molecular mechanism of action. MTT experiment showed XC-591 had significant anti-cancer activity on diverse cancer cells. Furthermore, XC-591 significantly suppressed the proliferation of 4T1 cells by colony formation assay. The in vivo results displayed that XC-591 could inhibit the growth and metastasis in 4T1 model. Moreover, histological analysis revealed that XC-591 treatment increased apoptosis, inhibited proliferation and angiogenesis in vivo. In addition, XC-591 did not contribute to obvious drug associated toxicity during the whole study. Molecular mechanism showed XC-591 could inhibit RhoGDI, activate caspase-3 and decrease phosphorylated Akt. The present data may be important to further explore this kind of new small-molecule inhibitor.