Symptoms, symptom clusters and associated factors among cancer patients receiving immune checkpoint inhibitor therapy: A cross-sectional survey.

PURPOSE: The purpose of this study was to explore the symptoms and symptom clusters and analyse associated factors among cancer patients receiving ICI therapy. METHODS: We analysed the data of 216 cancer patients who received immune checkpoint inhibitor therapy from the internal medicine unit of a university cancer centre in China. Participants were surveyed using the Eastern Cooperative Oncology Group Performance Score (ECOG PS) assessment, the ICI therapy symptom assessment scale, and demographic and disease characteristic questionnaires designed for this study. Exploratory factor analysis and multiple linear regression analysis were performed to analyse the data. RESULTS: The most common symptoms in patients with grade 1-2 symptom severity were fatigue (57.4%), itching (34.3%) and cough (33.3%), and those with grade 3-4 symptom severity were rash (7.9%), joint pain (6.9%), muscle soreness (6.5%) and fatigue (6.5%). Four symptom clusters were identified: nonspecific, musculoskeletal, respiratory and cutaneous (the cumulative contribution to the variance was 64.070%). ECOG PS, disease course and gender were significantly associated with the nonspecific symptom cluster (Adj R2 = 14.3). ECOG PS and disease course were significantly associated with the respiratory symptom cluster (Adj R2 = 8.9). ECOG PS, disease course and education level were significantly associated with the musculoskeletal symptom cluster (Adj R2 = 20.2). CONCLUSION: Cancer patients receiving ICI therapy experience various symptoms with apparent clustering. The factors associated with symptom clusters included gender, education level, ECOG PS and disease course. These findings would be useful for medical personnel to provide relevant interventions to promote symptom management of ICI therapy.

Simultaneous and sensitive detection of multiple small biological molecules by microfluidic paper-based analytical device integrated with zinc oxide nanorods.

In this work, ZnO nanorods (ZnO NRs) with different sizes were hydrothermally grown on the surface of Whatman filter paper for the fabrication of a microfluidic paper-based device (µPAD) for the simultaneous detection of glucose and uric acid. As dual enzymatic reaction was employed for the colorimetric detection in this µPAD, the presence of ZnO NRs promoted the enzyme immobilization thus significantly enhancing the colorimetric signal. The coffee ring effect was effectively conquered by the uniform distribution of ZnO NR as well as a specialized double-layered µPAD design. Meanwhile, two color indicators with distinct colors were used to provide complementary results to better quantify the concentration of the analytes by naked eye. As a result, two linear calibration curves were obtained for the detection of glucose (0.01-10 mmol L-1) and uric acid (0.01-5 mmol L-1), along with a LOD of 3 µmol L-1 for glucose and 4 µmol L-1 for uric acid, respectively. The practical usefulness of the proposed µPAD was further validated by the simultaneous analysis of glucose and uric acid in serum samples and urine samples.

Carbon nitride nanoparticles as ultrasensitive fluorescent probes for the detection of α-glucosidase activity and inhibitor screening.

In recent years, α-glucosidase inhibitors (AGIs) have played a significant role in the treatment of type II diabetes (T2D), so it is necessary to develop a reliable and sensitive method to find new AGIs. Herein, we establish a novel method based on fluorescent carbon nitride nanoparticles (CNNPs) for the sensitive detection of the activity of α-glucosidase (α-glu) and the screening of its inhibitors. A CNNP-based fluorescent probe is synthesized from green raw materials, urea and lysine, by a one-pot method. In the presence of α-glu, the substrate 4-nitrophenyl-α-d-glucopyranoside (pNPG) is hydrolyzed to generate 4-nitrophenol (pNP), leading to the fluorescence (FL) quenching of CNNPs due to the inner filter effect (IFE). On the other hand, the activity of α-glu is inhibited after the addition of AGIs, which turns on the FL of CNNPs. In this way, the detection of α-glu activity and the screening of AGIs are achieved. The linear range is 1.25-10.00 U L-1 with a limit of detection as low as 0.17 U L-1 and the IC50 values of two typical inhibitors (gallic acid and acarbose) are 813 µM and 465 µM, respectively. The CNNP probe is further applied for the determination of α-glu activity in human serum samples with satisfactory results.

A Comparative Study of Distinct Ocular Symptoms After Performing Laparoscopic Surgical Tasks Using a Three-Dimensional Surgical Imaging System and a Conventional Two-Dimensional Surgical Imaging System.

BACKGROUND AND PURPOSE: Stereoscopic imaging systems have improved the surgical accuracy and patient safety but have induced unwanted visual disturbance, nausea, and ocular symptoms simultaneously. We measured and compared visual discomfort and visual fatigue induced by three-dimensional (3D) surgical imaging system and two-dimentional (2D) surgical imaging system, respectively. METHODS: This study compared ocular symptoms and visual functions immediately after four laparoscopic tasks including pick beans, paper cut, pass the curved needle, and knot tying. Ten participants started with 3D laparoscopy, 9 participants with 2D laparoscopy on the first day, and reversed the laparoscopy for the participants on the second day. Before performing the tasks and immediately after performing the tasks for 1 hour, the participants underwent an interview with questions on ocular symptoms, and then received the systematic measurements of the visual functions objectively. The ocular symptoms were compared between the two groups, and the visual functions were compared in each group and between the two groups. RESULTS: When comparing the 3D laparoscopy group with the 2D laparoscopy group, symptom scores showed statistically significant differences in blurred vision during the task (z=-3.64, P=0.00), irritated or burning eyes (z=-2.17, P=0.03), dry eyes (z=-2.72, P=0.01), eyestrain (z=-3.11, P=0.00), headache (z=-3.20, P=0.00), discomfort in eyes (z=-3.74, P=0.00). The objective visual functional parameters such as distance exophoria (P=0.83), near exophoria (P=0.88), distance esophoria (P=0.93), near esophoria (P=0.80), the fusion range (P=0.09), the accommodative convergence/accommodation (P=0.56), and the tear film breakup time (P=0.48) had no significant difference between the two groups. CONCLUSIONS: When the passively polarized 3D surgical imaging system was compared with the 2D surgical imaging system, although subjective feelings were uncomfortable, there was no objective evidence to indicate that the 3D surgical imaging system resulted in an increment of visual fatigue. The visual fatigue and discomforts were moderate and could be tolerated by the surgeons.

Synergistic enhancement of cancer therapy using a combination of ceramide and docetaxel.

Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + DTX) and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and combination index (CI) assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31) and human breast carcinoma cell (MCF-7, CI = 0.48). The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01). The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

[Clinical characteristics and prognosis analysis of patients with LMP-1 positive Hodgkin's lymphoma after EBV infection].

This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.

Perceptual learning improves stereoacuity in amblyopia.

PURPOSE: Amblyopia is a developmental disorder that results in both monocular and binocular deficits. Although traditional treatment in clinical practice (i.e., refractive correction, or occlusion by patching and penalization of the fellow eye) is effective in restoring monocular visual acuity, there is little information on how binocular function, especially stereopsis, responds to traditional amblyopia treatment. We aim to evaluate the effects of perceptual learning on stereopsis in observers with amblyopia in the current study. METHODS: Eleven observers (21.1 ± 5.1 years, six females) with anisometropic or ametropic amblyopia were trained to judge depth in 10 to 13 sessions. Red-green glasses were used to present three different texture anaglyphs with different disparities but a fixed exposure duration. Stereoacuity was assessed with the Fly Stereo Acuity Test and visual acuity was assessed with the Chinese Tumbling E Chart before and after training. RESULTS: Averaged across observers, training significantly reduced disparity threshold from 776.7″ to 490.4″ (P < 0.01) and improved stereoacuity from 200.3″ to 81.6″ (P < 0.01). Interestingly, visual acuity also significantly improved from 0.44 to 0.35 logMAR (approximately 0.9 lines, P < 0.05) in the amblyopic eye after training. Moreover, the learning effects in two of the three retested observers were largely retained over a 5-month period. CONCLUSIONS: Perceptual learning is effective in improving stereo vision in observers with amblyopia. These results, together with previous evidence, suggest that structured monocular and binocular training might be necessary to fully recover degraded visual functions in amblyopia. Chinese Abstract.

Clinical effect of Maixuekang Capsule (脉血康胶囊) on long-term prognosis in patients with acute coronary syndrome after percutaneous coronary intervention.

OBJECTIVE: To study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (, MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention (PCI). METHODS: A total of 236 patients with acute coronary syndrome, who received successful PCI, were randomly assigned to a trial group (116 cases) and a control group (120 cases) according to random numbers; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms. In the trial group, the patients were treated with MKC combined with routine medication, and in the control group the patients were treated with routine medication. The therapeutic course for the two groups was 12 months and the follow-up was 12 months. The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein (hs-CRP) were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up. RESULTS: Compared with before PCI, the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI (P<0.05). They were significantly reduced after 30-day-treatment of MKC, showing statistical differences when compared with those in the control group (P<0.05). During the 12-month follow-up, the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group (6.9% vs. 12.5%, P<0.01). CONCLUSIONS: ADP-induced platelet aggregation function was significantly elevated after PCI. MKC improved the prognosis of patients with acute coronary syndrome, possibly through inhibiting the platelet aggregation, fighting against inflammation, and protecting the vascular endothelial function.

Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer.

The aim of our study was to develop hyaluronic acid-coated, paclitaxel-loaded, nanostructured lipid carriers (HA-NLCs) prepared via electrostatic attraction for delivering paclitaxel (PTX) to tumors overexpressing CD44. First, cationic PTX-NLC was prepared by melt emulsion technology. Then, PTX-NLC were coated with hyaluronic acid (HA). The in vitro release of PTX was evaluated by the dialysis method. This analysis showed that PTX was released more slowly from HA-NLC than from Taxol®. The in vitro cytotoxicity of HA-NLC was investigated using the MTT method in B16, CT26 and HCT116 cell lines. The results showed that the cytotoxicity of HA-NLC against these three cancer cell lines was superior to that of Taxol®. The in vivo antitumor effect, the pharmacokinetics and the tissue distribution of HA-NLC were all evaluated in B16-bearing Kunming mice. The results showed that HA-NLC was better tolerated and had increased antitumor activity in B16-bearing Kunming mice compared with Taxol®. Furthermore, HA-NLC could prolong the circulation time of PTX in blood and increase the accumulation of PTX in the tumor. Therefore, HA-NLC prepared via electrostatic attraction was an effective carrier for delivering PTX to tumors overexpressing CD44.

[A clinical analysis of 509 cases of sacroiliitis].

OBJECTIVE: To study the clinical features of sacroiliitis and differential diagnosis. METHODS: Totally 509 patients with chief complaints of back pain and diagnosed as sacroiliitis from January 2007 to January in Chinese PLA General Hospital were enrolled. The clinical manifestations, laboratory examinations, imaging and pathological data of the 509 patients were retrospectively analyzed. RESULTS: There were totally 406 male patients and 103 female patients. Among all 509 patients, 436 were diagnosed as ankylosing spondylitis (AS)/ spondyloarthropathy (SpA) , including 385 men. Thirty-six cases were diagnosed as sclerosing osteitis. Ten cases were diagnosed as sacroiliac joint degeneration. Ten cases were diagnosed as pyogenic sacroiliitis or sacroiliac joint tuberculosis. Four cases were diagnosed as diffuse idiopathic bone hypertrophy. Four cases were diagnosed as palmoplantar pustulosis arthritis. Four cases were diagnosed as metabolic bone disease. One case was diagnosed as sacroiliac joint gout. Four cases were diagnosed as neoplastic disease. HLA-B27 positive rate was 86.9% in AS/SpA. Erythrocyte sedimentation rate and C-reactive protein were increased mildly-to-moderately in AS/SpA patients. Erythrocyte sedimentation rate and C-reactive protein increased obviously in sacroiliac joint infection and tumor diseases. Imaging characteristics were sacroiliac joint bone destruction. Magnetic resonance imaging showed sacroiliac joint bone marrow edema, but range was not beyond anatomical structure in AS/SpA. CONCLUSIONS: Based on disease distribution of sacroiliitis, AS/SpA is predominant while non-ankylosing spondylitis is not uncommon. Differential diagnoses of sacroiliitis should be considered to avoid malpractice, especially in patients with negative HLA-B27.

Combined effect of atorvastatin and probucol on plasma cystatin C levels and severity of coronary lesion in patients with borderline coronary lesion.

BACKGROUND: The plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions. METHODS: One hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography. RESULTS: PcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment. CONCLUSIONS: Cystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.

[Genomic DNA extraction from hair sacs of pigs using modified phenol-chloroform method].

In referring to various methods for genomic DNA extraction from different tissues, we modified the classical phenol-chloroform procedure and reaction system for use in genomic DNA extraction from pig hair sacs. With the modified the phenol-chloroform method we successfully obtained high quality genomic DNA from pig hair sacs. Genomic DNA can be extracted from sacs of one to six pig hairs with satisfied quantity and quality for the need of PCR-based molecular ex-periment.

qCSF in clinical application: efficient characterization and classification of contrast sensitivity functions in amblyopia.

PURPOSE: The qCSF method is a novel procedure for rapid measurement of spatial contrast sensitivity functions (CSFs). It combines Bayesian adaptive inference with a trial-to-trial information gain strategy, to directly estimate four parameters defining the observer's CSF. In the present study, the suitability of the qCSF method for clinical application was examined. METHODS: The qCSF method was applied to rapidly assess spatial CSFs in 10 normal and 8 amblyopic participants. The qCSF was evaluated for accuracy, precision, test-retest reliability, suitability of CSF model assumptions, and accuracy of amblyopia screening. RESULTS: qCSF estimates obtained with as few as 50 trials matched those obtained with 300 Ψ trials. The precision of qCSF estimates obtained with 120 and 130 trials, in normal subjects and amblyopes, matched the precision of 300 Ψ trials. For both groups and both methods, test-retest sensitivity estimates were well matched (all R > 0.94). The qCSF model assumptions were valid for 8 of 10 normal participants and all amblyopic participants. Measures of the area under log CSF (AULCSF) and the cutoff spatial frequency (cutSF) were lower in the amblyopia group; these differences were captured within 50 qCSF trials. Amblyopia was detected at an approximately 80% correct rate in 50 trials, when a logistic regression model was used with AULCSF and cutSF as predictors. CONCLUSIONS: The qCSF method is sufficiently rapid, accurate, and precise in measuring CSFs in normal and amblyopic persons. It has great potential for clinical practice.

[Study on anisometropic amblyopia by simultaneously recording multifocal VEP and multifocal ERG].

OBJECTIVE: To investigate the characteristic changes of the retina, the visual pathway and the visual cortex in patients with anisometropic amblyopia by simultaneously recording multifocal VEP and multifocal ERG. METHODS: Pattern and flash simultaneously recording of the multifocal VEP and ERG of both eyes of 24 anisometropic amblyopes were recorded and the results were compared with those of 30 normal subjects. RESULTS: In different retinal areas the amplitudes of multifocal pattern VEP and ERG and second order kernel of multifocal flash VEP and ERG of the amblyopic eyes were reduced. In amblyopic eyes the latencies of mVEP were markedly prolonged while no changes of the mERG latencies were found. Amplitudes of first order kernel of multifocal flash VEP and ERG in amblyopic eyes were reduced while no changes in latencies. The abnormalities of multifocal pattern VEP waveforms in amblyopia were larger in central area than in peripheral and were correlated with the damage of visual acuity of the amblyopic eyes. Retinocortical time of multifocal pattern and the second order kernel of multifocal flash responses were prolonged in amblyopic eyes, while no changes were found for the first order kernel responses. CONCLUSION: The mVEP and mERG results revealed characteristic suggesting a malfunction of the retina, the visual pathway and the visual cortex in amblyopic patients.