Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Apoptosis gene reprograming of human peripheral blood mononuclear cells induced by radioiodine-131 (131I) irradiation.

Background & objectives: The nature of adaptable change of B-cell lymphoma-2 (BCL-2) and/or Bcl2-associated X protein (BAX) gene expression in the human peripheral blood mononuclear cells (PBMCs) irradiated by radioiodine in thyroid diseases therapy is not fully understood. In this study, the alternation of apoptotic gene expression was evaluated while the PBMCs collected from healthy volunteers were irradiated by the radioiodine-131 (131I). Methods: Fasting blood samples were obtained from healthy volunteers. PBMCs from group 0 to 6 were incubated and exposed to different doses of 131I in cell suspension for 6, 12, 24 and 48 h. The apoptosis rates and expression of BCL-2 and BAX genes of PBMCs were examined. Results: The apoptosis rate in the human PBMCs was gradually enhanced after six hour irradiation. The values of BCL-2 and BAX gene expression in groups 1-6 were higher than in group 0 within 6 h of irradiation, and then, these were decreased gradually from 6 to 12 h. BCL: -2 gene expression increased in groups 1-3 after 12 h irradiation, but there was no difference in groups 4-6. The ratio of BCL-2/BAX gene expression among groups 4-6 gradually decreased during the period from 6 to 12 h, and it was significantly lower than in the group 0 at 12, 24 and 48 h. Interpretation & conclusions: The expression of BCL-2 and BAX genes was initially upregulated following irradiation. Later, the balance of BCL-2/BAX genes expression was adjusted, and then, PBMCs underwent apoptosis at higher doses of radiation.

Proportion of neuropathic pain in the back region in chronic low back pain patients -a multicenter investigation.

Neuropathy can contribute to low back pain (LBP) in the region of the back. Our study investigated the proportion of neuropathic pain (NP) in low back region in chronic LBP patients from multicenter and clinics in China and identified associated factors. Assessment was made using a questionnaire and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS, only tested in low back region), as well as Quantitative Sensory Testing (QST, merely applied to the low back region), the Hospital Anxiety and Depression Scale (HADS) and the Oswestry Disability Index (ODI). Our questionnaire collected demographic information, behavioral habits and medical records. 2116 outpatients over 18 years old complaining of LBP lasting more than 3 months were enrolled in this study. The NP proportion in low back region in chronic LBP patients was 2.8%. Multivariable logistic regression analysis showed that histories of lumbar surgery, abdominal or pelvic surgery, and drinking alcohol were independent positive predictors for LBP of predominantly neuropathic origin (LBNPO), while history of low back sprain and frequently carrying weight as independent negative predictor. Using these parameters may help the identification of patients with chronic LBP likely to develop NP leading to improved treatment outcomes.

Hyperuricemia is associated with atrial fibrillation prevalence in very elderly - a community based study in Chengdu, China.

Hyperuricemia is a risk factor for cardiovascular diseases. However, in very elderly, the relationship between hyperuricemia and the prevalence of atrial fibrillation (AF) is not clear. This study aimed to investigate hyperuricemia and the risk of AF in community very elderly. In this cross-sectional study, 1056 very elderly in community were enrolled. Serum uric acid (SUA) were measured and rest 12-lead electrocardiogram was performed. Multiple logistic regression models were used to explore risk factors for AF in very elderly. Finally, 1038 participants were included in analysis and the mean age of the study participants were 83.6 ± 3.4 years (age range 80-100 years). The mean SUA level was 350.1 ± 84.5 µmol/L. The estimated prevalence of AF was 5.3%, and there was no significant sex difference (5.8% for men and 4.8% for women, p = 0.401). Multiple logistic regression found that participants with hyperuricemia (SUA >416 µmol/L in men and >357 µmol/L in women) had a higher risk (odds ratio: 2.080, 95% confidence interval: 1.103-4.202, P = 0.007) of suffering AF in very elderly Chinese. In conclusion, AF is relatively frequent in this community very elderly Chinese in Chengdu. Hyperuricemia is associated with the prevalence of AF in general very elderly.

Temporal trends in Prevalence, Awareness, Treatment, and Control of Hypertension from 2000 to 2010 in Chengdu, China.

This study aimed to describe trends in prevalence, awareness, treatment, and control in hypertension in Chengdu from 2000 to 2010. Two community-based cross sectional surveys were conducted among those aged 40-79 years in 2000 (n = 4850) and 2010 (n = 5456). Demographic characteristics, blood pressure (BP) and associated risk factors were examined. Mean systolic and diastolic BP increased from 117.8 ± 33.9 to 132.1 ± 21.2 mmHg (P < 0.001), and 75.3 ± 19.1 to 79.3 ± 11.2 mmHg (P < 0.001) over past decade, respectively. The prevalence of hypertension increased from 27.7 to 29.4% (P < 0.001). Awareness increased from 37.7 to 42.5% (P < 0.001). The overall treatment rate increased from 20.9 to 28.0% (P < 0.0001), while among subjects aware of hypertension, treatment increased from 46.9 to 65.8% (P < 0.001). In hypertensives, control increased from 6.8 to 6.9% (P = 0.6684). Nevertheless, in hypertensives aware and treated, control decreased from 32.5 to 24.3% (P = 0.020). Hypertension prevalence increased in the last decade, while awareness, treatment and control remained considerably low in Chengdu.

Prevalence, awareness, treatment, and control of hypertension among very elderly Chinese: results of a community-based study.

The epidemiologic distribution of hypertension among very elderly Chinese is still not clear. This study aimed to investigate the prevalence, awareness, treatment, and control rate of hypertension among very elderly in Chengdu. From May 2013 to May 2015, a total of 1056 participants from 20 residential communities were sampled. Standard face-to-face interviews, physical examinations, and biochemical analysis were undertaken. Participants had a mean age of 83.6 ± 3.4 years (range: 80-100), and 49.8% were men. Mean systolic blood pressure (BP) and diastolic BP were 146.4 ± 20.6 and 74.1 ± 11.9 mm Hg, respectively, and both of the highest BP levels were among participants aged 80-84 years. Mean pulse pressure was 72.5 ± 17.1 mm Hg, and the highest pulse pressure level was among participants aged 90 years and older. The overall estimated hypertension prevalence was 75.3% (95% confidence interval: 72.6%-77.9%), and among overall participants, 51.9% were aware of their hypertensive condition and 45.5% were treated. However, only 18.1% of hypertensive participants were controlled (BP < 140/90 mm Hg). Among very elderly Chinese in Chengdu, the prevalence of hypertension is predominantly high, whereas awareness, treatment, and control rates are considerably low. Effective primary and secondary prevention strategies are needed.

Hyperuricemia is associated with cardiovascular diseases clustering among very elderly women - a community based study in Chengdu, China.

Cardiovascular epidemiological features among very elderly Chinese are still uncertain. This study aimed to describe the distribution of cardiovascular diseases and sex difference, and investigate potential risk factors for diseases clustering among very elderly Chinese. From May 2013 to May 2015, a total of 1056 very elderly were sampled in this cross-sectional study. Demographic characteristics collection, physical examination and biochemical analysis were performed. Totally, 1038 participants (men: 49.8%) with a median age of 83.0 years (age range: 80.0-100.0 years) were included. In this very elderly group, the prevalences of hypertension, diabetes mellitus, renal dysfunction, hyperuricemia, obesity, visceral obesity, and hypercholesterolaemia were 76.9%, 20.0%, 23.3%, 33.0%, 9.4%, 54.5% and 35.8%, respectively. About 17.5% of very elderly (men vs. women: 15.1% vs 19.8%, p = 0.007) have ≥3 cardiovascular diseases clustering. Logistic analysis found that hyperuricemia (odds ratio 3.850, 95%CI 2.189-6.770) was associated with of cardiovascular diseases clustering among very elderly women. Prevalences of prehypertension, hyperuricemia, visceral obesity and dyslipidaemia are apparent in very elderly women, while diabetes mellitus, renal dysfunction are common in very elderly men. Women are more likely to have ≥3 cardiovascular diseases. Hyperuricemia is associated with cardiovascular diseases clustering among very elderly women.

Immunoglobulin G4-Related Lung Disease Presenting as Lung Cavitating Mass and Mimicking Lung Cancer.

Immunoglobulin G4-related lung disease (IgG4-RLD) is a disease in which abundant activated IgG4-positive plasma cells and lymphocytes infiltrate lung tissues with high 18F-fluorodeoxyglucose uptake. Although various forms of radiologic features of IgG4-RLD have been reported, cavitating mass is a rare imaging feature and should be differentiated from cancer. Therefore, in this article, we report two cases both with unprovoked cough, bloody sputum and presenting quite similar cavitating lesions with high 18F-fluorodeoxyglucose uptake on positron emission tomography/ computed tomography, one of which diagnosed as IgG4-RLD and the other as lung cancer based on biopsy eventually. The awareness of the imaging features of IgG4-RLD and lung cancer described in the present study may help physicians to distinguish one from the other. IgG4-RLD should be considered in the differential diagnosis of cavitary lung lesions.

Nanoemulsion of D-limonene in water system prepared by ultrasonic emulsification.

D-Limonene is a component of essential oil extracted from citrus fruits. This component has shown chemopreventive and therapeutic activity against a wide variety of experimental tumors, but D-limonene is unstable and lose its lemon-like flavor under normal storage condition, and it is almost insoluble in water. Therefore, studying the formation of nanoemulsion in D-limonene in water system is probably a good method to prevent the oxidation degradation of D-limonene. For the purpose of our study, we used mixed surfactant to form D- limonene-in-water emulsion, and found the best formula for forming nanoemulsion droplets with specified hydrophilic-lipophilic balance (HLB) value and droplet size. The results demonstrated that nanoemulsion droplets formed at So ratio of 0.4 and applied power of 18 W for 120 s under mixed surfactant at HLB values 12 and had droplet size of 20-50 nm.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis.

BACKGROUND: There is not a general agreement regarding antiarrhythmic effects on atrial fibrillation (AF) of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). This study was to assess whether ACEIs and ARBs could decrease the incidence of AF. MATERIALS AND METHODS: Medline, Embase and Cochrane Library databases were searched for trials reported from 1950 to May 2009. Search terms included 'randomized controlled trial (RCT), controlled clinical trials, random allocation' and medical subject headings that included all spellings of ACEIs and ARBs agents, 'atrial fibrillation' and 'atrial flutter'. Randomized, controlled human trials of ACEIs or ARBs reporting AF were included. Data were extracted independently by two reviewers using a predefined data extraction sheet, including study quality indicators. Meta-analysis and subgroup analyses were carried out with a random effects model. RESULTS: Twenty-one trials including 91,381 patients and 5730 AF events were identified. Overall, ACEIs/ARBs reduced the relative risk (c) of AF by 25%. In primary and secondary prevention, ACEIs/ARBs decreased the incidence of AF by 24% and 27%, respectively. Patients with hypertension (RR: 0·71, 95%CI: 0·54-0·92), patients with chronic heart failure (RR: 0·58, 95%CI: 0·39-0·87) and those with AF (RR: 0·71, 95%CI: 0·52-0·96) benefited from ACEIs/ARBs treatment. CONCLUSIONS: ACEIs/ARBs are effective for primary prevention and secondary prevention of AF. They decrease the incidence of AF especially in patients with hypertension, patients with chronic heart failure and those with AF.

[An epidemiological study of abnormal glucose metabolism and its risk factors among middle and aged population with hypertension in Chengdu area].

OBJECTIVE: To explore the epidemiological status of abnormal glucose metabolism and its influential factors among middle and aged population with hypertension in Chengdu area. METHODS: In 2008, after adopting the methods of stratified cluster sampling, the authors investigated 4685 subjects of the middle and aged population between the age of 40 - 79 in Chengdu urban and rural area by checking blood pressure and oral glucose tolerance test (OGTT). Patients with previously known diabetes mellitus (DM) were only asked to perform fasting glucose and to carry out a questionnaire. Comparison of the prevalence rates of abnormal glucose metabolism in hypertensive and non-hypertensive subjects was carried out. The prevalence rates of isolated impaired glucose tolerance (I-IGT) and isolated postprandial hyperglycemia (IPH) among middle and aged subjects with hypertension were acquired and the influential factors of abnormal glucose metabolism among middle and aged subjects with hypertension were analyzed. RESULTS: The prevalence rate of abnormal glucose metabolism in the hypertensive subjects was obviously higher than that in the non-hypertensive subjects; without using OGTT, 72.9% of the pre-diabetic and 54.4% of the new diagnosed DM patients would remain undiagnosed if fasting plasma glucose detection was used alone. Age, diabetic history of first degree relatives, overweight or obesity were the risk factors for the development of abnormal glucose metabolism among middle and aged male subjects with hypertension in Chengdu area. Exercise training and high education level were the protective factors. Age, diabetic history of first degree relatives, abdominal obesity and hypertriglyceridemia were the risk factors for the development of abnormal glucose metabolism among middle and aged female subjects with hypertension in Chengdu area. CONCLUSIONS: More than 50% of middle and aged subjects with hypertension in Chengdu area has accompanying abnormal glucose metabolism. OGTT easily discloses the abnormal status and should be a routine procedure in the diagnosis of pre-diabetes or DM in such population. Appropriate exercise, learning diabetes-related knowledge to take reasonable lifestyle, and intervention of metabolic factors such as overweight or obesity are advised. Abdominal obesity and hypertriglyceridemia play important roles in leading to abnormal glucose metabolism among middle and aged population with hypertension.

[Development of evaluation tool for the risk level of abnormal glucose metabolism morbidity in middle-aged and elder populations].

OBJECTIVE: To develop the evaluation tool for the risk level of abnormal glucose metabolism morbidity in the middle-aged and elder populations. METHODS: By the stratified cluster sampling method, a survey was conducted in middle-aged and elder populations aged 40 - 70 years old in urban and rural areas of Chengdu during April-November 2008. The parameters included blood pressure, fasting blood glucose, blood glucose after oral administration of 75 g glucose, blood lipid, blood uric acid, height, body weight and waistline, etc. A total of 5205 valid copies of questionnaires were obtained. A discriminant analysis and a multifactorial logistic regression analysis were conducted. The quantitative scoring system was established and the ROC analysis conducted to screen the boundary point of the quantitative scoring system. The discriminant performance of simple scoring model was conducted in 336 subjects for physical examination. RESULTS: The accuracies of discriminant analysis in male and female models were 79.04% and 81.35% respectively. The simple male scoring mode included the following eight parameters: age, physical work intensity, parental history of diabetes mellitus, sibling's history of diabetes mellitus, BMI index, existing abdominal obesity and history of hypertension. The simple female scoring mode included the following eight parameters: age, physical work intensity, physical training, parental history of diabetes mellitus, sibling's history of diabetes mellitus, BMI index, existing abdominal obesity, history of hypertension, number of parturition and history of gestational diabetes mellitus. The ROC AUCs were 0.701 and 0.728 in male and female models respectively. During applications in other populations, the sensitivity and specificity of the male model were 86.86% and 65.12% while those of female model 88.89% and 72.97% respectively. CONCLUSIONS: The newly developed evaluation tool for the risk level of abnormal glucose metabolism morbidity in middle-aged and elder populations is both simple and practical. With an excellent practicability; it may be used to screen abnormal glucose metabolism in middle-aged and elder populations.

Effect of neurolytic celiac plexus block guided by computerized tomography on pancreatic cancer pain.

The efficacy of neurolytic coeliac plexus block (NCPB) guided by computerized tomography (CT) was compared with pharmacological therapy in the treatment of pain due to pancreatic cancer. The study involved 56 patients who were placed randomly in either a NCPB group and pharmacological therapy group. At day 1, 7, and 14, the visual analogue scale (VAS) pain scores of the NCPB group were significantly lower than those of the pharmacological therapy group (P < 0.01), with values of 1.3 +/- 0.8 versus 4.1 +/- 0.9, 1.7 +/- 1.1 versus 3.1 +/- 1.1, and 2.0 +/- 1.1 versus 2.9 +/- 0.6, respectively. However, the differences in the improvement of quality of life (QOL) between two groups were not statistically significant. Moreover, the dose of opioid was significantly lower in the patients of group 1 than those of group 2, while the complications related to NCPB were transient. We therefore concludes that CT-guided NCPB with alcohol is an effective and safe modality in the management of intractable pancreatic cancer pain.

Hippocampus bcl-2 and bax expression and neuronal apoptosis after moderate hypothermic cardiopulmonary bypass in rats.

Using a rat model of moderate hypothermic (26 degrees C-28 degrees C) cardiopulmonary bypass (CPB) with hemodilution, we investigated hippocampal apoptotic gene expression and neuronal apoptosis up to 6 h after CPB. The CPB was performed on male rats (380-400 g) under general anesthesia with isoflurane and fentanyl. The right atrium and tail artery were cannulated, and a peristaltic pump and membrane oxygenator were used for CPB. Two groups were studied: Group 1 consisted of fasted rats (n = 15) subjected to 60 min of moderate hypothermic nonpulsatile CPB; Group 2 consisted of sham-operated rats (n = 15). At 1 h after CPB, in 6 rats per group, hippocampus was processed for the apoptotic gene (bcl-2 and bax) messenger RNAs detection by reverse transcriptase polymerase chain reaction, and messenger RNA expression was determined by the ratio of the polymerase chain reaction product of bcl-2 or bax to the beta-actin gene. At 6 h after CPB, in 6 rats per group, hippocampus expression of Bcl-2 and bax protein was determined by immunohistochemistry, and neuronal apoptosis was detected by TUNEL. At 6 h after CPB, in three rats per group, changes in hippocampal CA1 neuronal ultra structure were determined with electron microscopy. Group 1 had increased ratios of bcl-2/beta-actin, bax/beta-actin, and bax/bcl-2 mRNA at 1 h after CPB (bcl-2/beta-actin, 0.82 +/- 0.14 versus 0.63 +/- 0.07; P = 0.03; bax/beta-actin, 1.04 +/- 0.14 versus 0.56 +/- 0.03; P = 0.00; bax/bcl-2, 1.31 +/- 0.12 versus 0.84 +/- 0.09; P = 0.02; Group 1 versus Group 2, respectively). Group 1 had increased bcl-2 and bax protein expression in hippocampal CA1 region at 6 h after CPB (bcl-2, 0.18 +/- 0.05 versus 0.09 +/- 0.01; P = 0.02; bax, 0.20 +/- 0.06 versus 0.04 +/- 0.02; P = 0.01; Group 1 versus Group 2, respectively). Group 1 had increased TUNEL staining in hippocampus CA1 at 6 h after CPB (0.14 +/- 0.02 versus 0.03 +/- 0.01; P = 0.00; Group 1 versus Group 2, respectively). In Group 1 CA1 hippocampus neurons, ultra-structural changes consistent with apoptosis occurred. In rats, moderate hypothermic CPB with hemodilution is associated with CA1 hippocampus bax and bcl-2 gene expression and neuronal apoptosis during the early post-CPB recovery period.