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Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. Methods: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. Results: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65–10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63–6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24–4.99) were more likely to follow national guidelines for neurosyphilis treatment. Conclusion: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

Alzheimer's disease (AD), as the primary cause of dementia, has seriously affected millions of people worldwide and brought a very heavy financial and social burden. With the growth of population and aging, the situation will worsen unless efficacious drugs are found to reverse, stop, or even slow down disease progression. More and more evidence has demonstrated that amyloid-β (Aβ) aggregation is an upstream causative factor in AD pathogenesis and then triggers a slew of pathological events. Furthermore, the concentrated redox metal ions in the AD brain, especially Cu(II), can significantly exacerbate Aβ aggregation and contribute to the formation of neurotoxic reactive oxygen species (ROS). Therefore, the inhibition of Aβ aggregation and relief of amyloidosis-initiated neurotoxicity play a critical role in AD treatment. Until now, several methods have been proposed to modulate Aβ aggregation, such as developing aggregation inhibitors to interfere with Aβ assembly via noncovalent interactions, copper chelators to cut off metal-accelerated Aβ aggregation and concomitant cytotoxicity, photooxidation to reduce the hydrophobicity and aggregation tendency of Aβ, thermal dissociation to disrupt amyloid aggregates susceptible to temperature, degradation with artificial protease to fracture the Aβ peptide into small fragments, and the clearance of peripheral Aβ to bypass the obstruction of the BBB and reduce the Aβ burden.In this Account, we focus on our contributions to the development of Aβ-targeted multifunctional molecules and nanoparticles, emphasizing the diversified strategies and synergistic therapeutic effects. These therapeutic agents possess the following multifunctionalities: (1) compared with frequently used aggregation inhibitors restricted by intrinsically feeble and sensitive noncovalent interactions, multifunctional agents can efficiently block Aβ aggregation by exploiting two or more Aβ-specific inhibition strategies simultaneously; (2) apart from regulating Aβ aggregation, multipronged agents can also target and modulate other pathological factors in AD pathogenesis, such as increased oxidative stress, abnormal copper accumulation, and irreversible neuron loss; (3) multifunctional platforms with both diagnostic and therapeutic modalities through integrating in situ imaging, real-time diagnostics, a multitarget direction, stimuli-responsive drug release, and the blood-brain barrier (BBB) translocation features are instrumental in improving drug levels at trouble sites, diminishing off-target adverse reactions, evaluating therapeutic effects, and averting overtreatment.Given the fact that amyloid aggregation, local inflammation, and metal dyshomeostasis are universal biomarkers shared by various neurodegenerative disorders, this Account provides a perspective for the evolution of customized therapeutic agents with multiple reactivities for other neurodegenerative diseases. In addition, recent studies have indicated that Aβ aggregates can enter the nucleus and induce DNA damage and anomalous conformational transition. We also explore the influences of DNA on the biological effects of Aβ aggregates.

Idiopathic short stature (ISS) is a main reason for low height among children. Its exact aetiology remains unclear. Recent findings have suggested that the aberrant expression of circRNAs in peripheral blood samples is associated with many diseases. However, to date, the role of aberrant circRNA expression in mediating ISS pathogenesis remains largely unknown. The up‐regulated circANAPC2 was identified by circRNA microarray analysis and RT‐qPCR. Overexpression of circANAPC2 inhibited the proliferation of human chondrocytes, and cell cycle was arrested in G1 phase. The expressions of collagen type X, RUNX2, OCN and OPN were significantly down‐regulated following circANAPC2 overexpression. Moreover, Von Kossa staining intensity and alkaline phosphatase activity were also decreased. Luciferase reporter assay results showed that circANAPC2 could be targeted by miR‐874‐3p. CircANAPC2 overexpression in human chondrocytes inhibits the expression of miR‐874‐3p. The co‐localization of circANAPC2 and miR‐874‐3p was confirmed in both human chondrocytes and murine femoral growth plates via in situ hybridization. The rescue experiment demonstrated that the high expression of miR‐874‐3p overexpression antagonized the suppression of endochondral ossification, hypertrophy and chondrocyte growth caused by circANAPC2 overexpression. A high‐throughput screening of mRNA expression and RT‐qPCR verified SMAD3 demonstrated the highest different expressions following overcircANAPC2. Luciferase reporter assay results indicated that miR‐874‐3p could be targeted by Smad3, thus down‐regulating the expression of Smad3. Subsequent rescue experiments of SMAD3 further confirmed that circANAPC2 suppresses endochondral ossification, hypertrophy and chondrocyte growth through miR‐874‐3p/Smad3 axis. The present study provides evidence that circANAPC2 can serve as a promising target for ISS treatment.

ObjectivesTo evaluate the up-to-date epidemiology of diabetes in northeast China.MethodsThe cross-sectional study was conducted between September 2017 and March 2019 using a multistage, stratified and cluster random sampling method. 18 796 participants (28.9% urban and 71.1% rural) aged ≥40 years were enrolled. Diabetes and pre-diabetes were diagnosed according to the history, fasting plasma glucose (FPG) and glycosylated haemoglobin A1c (HbA1c) levels.ResultsThe prevalence of diabetes was 17.1%, higher in urban than in rural residents (20.2% vs 15.8%, pConclusionA considerable burden of diabetes was observed in northeast China, with high percentage of untreated diabetes, high prevalence of pre-diabetes, high overall FPG level and multiple uncontrolled risk factors in patients with diabetics. Therefore, region-specific strategies on prevention and management of diabetes should be emphasised.

Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes. Herein, a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles (NPs) (SNP(I)) together with glucose oxidase (GOx)- and catalase (CAT)-loaded pH-insensitive NPs (iSNP(G+C)) is constructed for transcutaneous glucose-responsive insulin delivery. SNP(I) are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer, and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C) under hyperglycemic conditions. CAT in iSNP(G+C) can further consume excess H2O2 generated during GOx oxidation, and thus reduce the risk of inflammation toward the normal skin. The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivo studies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.

Summary Background and aims Immune response against hepatitis B virus (HBV) infection is an important risk factor for the development of hepatocellular carcinoma (HCC). Studies have reported that interleukin 22 (IL-22) exhibits both protective and pathological properties in liver diseases. Our aim was to explore the importance of IL-22 in the development of HCC, and to characterize the relationship between IL-22 levels and the prognosis of HCC. Methods Totally, 136 liver biopsy specimens from 46 patients with chronic hepatitis B (CHB), 37 with atypical hyperplasia (AH), 53 with HCC, patient-matched tumors and peritumoral surgical specimens from 56 HCC patients included in the study. The expression of IL-22 and CD8 was evaluated by immunochemistry. Corresponding serum samples were collected from 30 CHB, 30 AH, and 30 HCC patients. IL-22 expression was determined by an enzyme linked immunosorbent assay. Results Liver-infiltrating IL-22+ cells increased in a stepwise manner from CHB to AH and HCC (CHB vs. AH, P = 0.002; AH vs. HCC, P = 0.010), whereas a decreasing trend was observed for CD8+ T cells (CHB vs. AH, P = 0.031; AH vs. HCC, P = 0.652). Serum IL-22 levels also increased from CHB to AH and HCC (CHB vs. AH, P = 0.024; AH vs. HCC, P = 0.026). Tumor-infiltrating IL-22+ cells and serum IL-22 were associated with histologic grade (P = 0.024 and P = 0.033). Additionally, CD8+ T cells correlated with tumor size (P = 0.032). Furthermore, the high intratumoral IL-22+ cell group and high serum IL-22 group showed lower overall survival (OS; P = 0.001, P = 0.017) and disease-free survival (DFS; P = 0.005, P Conclusions These findings indicate that IL-22 promotes the progression of HCC in CHB patients. High tumor-infiltrating IL-22+ cells and serum IL-22 levels are thought to be unfavorable prognostic indicators for HCC.

Background Cardiopulmonary bypass (CPB) with high-priming volume can significantly activate the inflammatory response and increse the usage of packed red blood cells (PRBCs). As risks and complications related to transfusions are increasing, many cardiac centers are focusing on reducing the priming volume of CPB. In our center, efforts have also been made to reduce the priming volume, and the effects of CPB with low-priming volume on clinical outcomes in children undergoing congenital heart disease (CHD) surgery were investigated in this study to provide referential experiences for pediatric CPB. Methods The clinical case data of 158 children undergoing CHD surgery with CPB were collected. The children were divided into the low-priming-volume group (group A, n = 79) and the traditional group (group B, n = 79) according to the priming volume. The amount of PRBCs transfused, the postoperative hematological test results and the clinical outcomes of the two groups were compared by the independent sample t-test or the chi-square test. Results The amount of PRBCs transfused during CPB and during the whole operation were significantly lower in group A than in group B (p p p Conclusions The usage of PRBCs in CPB with low-priming volume decreased significantly, but the postoperative Hb concentration and platelet count could still be maintained at a high level, improving the use efficiency of PRBCs. CPB with low-priming volume did not affect the postoperative recovery of patients, so it is worthy of continuous promotion and optimization.

Objective:To gain more comprehensive understanding of metabolic syndrome (Mets) among in general Chinese population.Design:Cross-sectional study. Mets was defined by three widely accepted definitions including modified Adults Treatment Panel (ATP) III criteria, International Diabetes Federation (IDF) criteria and harmonized definition. Risk factors were evaluated by using multivariate logistic regression.Setting:Nineteen rural villages in northeast China.Participants:The survey was conducted in September 2017 and May 2018 on 10 926 individuals.Results:According to modified ATP III criteria, IDF criteria and harmonised definition, the overall prevalence of Mets was 41·3 % (95 % CI 40·3, 42·2), 34·2 % (95 % CI 33·2, 35·1) and 44·1 % (95 % CI 43·1, 45·1), respectively. Females had a higher prevalence, and elevated blood pressure was the most frequent. Age, female sex, non-peasant worker, higher BMI and lower-annual income were independent risk factors of Mets in all three definitions (all ps Conclusions:Mets is highly prevalent in rural areas of northeast China. Its independent risk factors include higher age, female sex, non-peasantry worker, higher BMI and lower-annual income. Modified ATP III criteria and harmonised definition may be superior definitions of Mets.

The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective program to prevent and treat for the novel coronavirus pneumonia. In view of Traditional Chinese Medicine has accumulated a solid theoretical foundation of plague in ancient and recent decades. Meanwhile, Traditional Chinese Medicine can provide the more effective and personalized treatment via adjusting the specific medicine for each patient based on the different syndromes. In addition, TCM often has different effect on the distinct stages of diseases, contributing to the prevention, treatment and rehabilitation. Nowadays, TCM has exhibited decent effect in the in the fight against NCP. Therefore, it is convinced that Traditional Chinese Medicine is an effective treatment for 2019 novel coronavirus pneumonia.

Background To investigate the status of hypertension and related risk factor disparities between urban and rural areas of northeast China. Methods A multi-stage, stratified, and cluster random sampling method was used to conduct the cross-sectional survey in Liaoning Province in 2017-2019. Finally, included 18,796 participants (28.9% urban, 71.1% rural) aged ≥40 years. The prevalence and control rate of hypertension were estimated based on Chinese hypertension guidelines and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Results The mean age of the population was 60.4±9.9 years, and 61.0% were women. The overall prevalence of hypertension was 56.8%. Compared to urban areas, hypertension was more prevalent, but the awareness, treatment, and control rates were lower in rural areas (59.2 vs 50.2, 52.5% vs 47.0%, 46.9% vs 34.9%, and 11.4% vs 3.7%, P

Objective. To investigate the epidemiological features of obesity in rural Northeast China. Design. This was a 2017–2018 cross-sectional study of 10,891 participants aged ≥40 years that was designed to investigate the prevalence of obesity in rural areas of Liaoning Province. Demographic data, biochemical parameters, and physical examinations were completed by well-trained personnel. Logistic regression analyses were then carried out to investigate independent risk factors and associated cardiometabolic comorbidities of obesity. Results. The proportions of general obesity only, central obesity only, and combined obesity were 1.0%, 31.3%, and 17.4%, respectively. Overall, 49.8% of our subjects were obese. Female gender, being married, being separated/divorced/widowed, or eating more meat were significantly associated with obesity. Smoking, higher family income, or regular physical exercise were negatively associated with obesity. General obesity only was significantly correlated with hypertension, diabetes, and high triglycerides (OR = 2.79, OR = 2.79, and OR = 3.37, resp.). General obesity only was irrelevant to high total cholesterol, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol, although central obesity only, or combined obesity, was relevant to these factors. Prehypertension and prediabetes showed a positive association with different types of obesity. Conclusions. We identified a high prevalence of general and central obesity in rural Northeast China, with similar independent risk factors. Participants with combined obesity had the highest risk of cardiometabolic comorbidities, indicating that the combined use of both waist circumference and body mass index is useful in practice.

Lymph nodes (LNs) are normally the primary site of tumor metastasis, and effective delivery of chemotherapeutics into LNs through systemic administration is critical for metastatic cancer treatment. Here, we uncovered that improved perfusion in a primary tumor facilitates nanoparticle translocation to LNs for inhibiting tumor metastasis. On the basis of our finding that an iCluster platform, which undergoes size reduction from ∼100 nm to ∼5 nm at the tumor site, markedly improved particle perfusion in the interstitium of the primary tumor, we further revealed in the current study that such tumor-specific size transition promoted particle intravasation into tumor lymphatics and migration into LNs. Quantitative analysis indicated that the drug deposition in LNs after iCluster treatment was significantly higher in the presence of a primary tumor in comparison with that after primary tumor resection. Early intervention of metastatic 4T1 tumors with iCluster chemotherapy and subsequent surgical resection of the primary tumor resulted in significantly extending animal survival, with 4 out of the 10 mice remaining completely tumor-free for 110 days. Additionally, in the more clinical relevant late metastatic model, iCluster inhibited the metastatic colonies to the lungs and extended animal survival time. This finding provides insights into the design of more effective nanomedicines for treating metastatic cancer.

ObjectiveIdiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS.MethodsFrozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experimentsin vitrowere used to further explore the effects of crucial proteins on endochondral ossification.ResultsA total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p ConclusionOur study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.

BackgroundPatients with connective tissue disease, such as dermatomyositis (DM), and positive anti-TIF1γ self-antibodies are commonly diagnosed with malignant tumors as a comorbidity. The relationship between anti-TIF1γ self-antibodies and existing malignant tumors has been confirmed by several reports. However, interstitial pneumonia with autoimmune features (IPAF) cases with a positive anti-TIF1γ self-antibody developing to solid malignant tumors are rarely reported now.Case presentationHerein, we presented an IPAF patient with anti-TIF1γ self-antibodies. No evidence of malignant tumors was found at the initial visit. However, the patient had developed stage IVB lung squamous cell carcinoma at the 1-year follow-up review.ConclusionsAltogether, this report described a rare case of IPAF patient with anti-TIF1γ self-antibodies developed to advanced lung squamous cell carcinoma in 1 year. The present case highlights more frequent imaging examinations to identify the occurrence of malignant tumors as early as possible in IPAF patients with positive anti-TIF1γ self-antibodies.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a low survival rate. The therapeutic effect of chemotherapy and immunotherapy for PDAC is disappointing due to the presence of dense tumor stroma and immunosuppressive cells in the tumor microenvironment (TME). Herein, a tumor-penetrating nanoparticle is reported to modulate the deep microenvironment of PDAC for improved chemoimmunotherapy. The tumor pH-sensitive polymer is synthesized by conjugating N,N-dipentylethyl moieties and monomethoxylpoly(ethylene glycol) onto PAMAM dendrimer, into whose cavity a hydrophobic gemcitabine (Gem) prodrug is accommodated. They self-assemble into nanoparticles (denoted as SPN@Pro-Gem) with the size around 120 nm at neutral pH, but switch into small particles (≈8 nm) at tumor site to facilitate deep delivery of Gem into the tumor parenchyma. In addition to killing cancer cells that resided deeply in the tumor tissue, SPN@Pro-Gem could modulate the TME by reducing the abundance of tumor-associated macrophages and myeloid-derived suppressor cells as well as upregulating the expression level of PD-L1 of tumor cells. This collectively facilitates the infiltration of cytotoxic T cells into the tumors and renders checkpoint inhibitors more effective in previously unresponsive PDAC models. This study reveals a promising strategy for improving the chemoimmunotherapy of pancreatic cancer.

Objective To investigate whether ECG left ventricular hypertrophy (ECG-LVH) has prognostic value independent of echocardiography LVH (Echo-LVH). Methods Participants (N = 9744, mean age, 53.81 ± 10.49 years and 45.5% male) from the Northeast China Rural Cardiovascular Health Study were included. Associations between Echo-LVH (sex-specific left ventricular mass normalized to BSA) and ECG-LVH (diagnosed using the Cornell-voltage duration product) and adverse outcomes were evaluated using Cox regression. The value of ECG-LVH for predicting adverse events was evaluated by reclassification and discrimination analyses. Results Median follow-up was 4.65 years; 563 participants developed incident stroke or coronary heart disease (CHD) and 402 died. Compared with participants without either condition, those with both Echo-LVH and ECG-LVH had a significantly increased risk of incident stroke or CHD (hazard ratio, 2.42; 95% confidence interval, 1.82-3.22) and mortality (2.58; 1.85-3.60). ECG-LVH remained an independent risk factors for both outcomes when ECG-LVH and Echo-LVH were included in the model as separate variables [incident stroke or CHD (1.43; 1.14-1.79); mortality (1.41; 1.08-1.84)]. Reclassification and discrimination analyses indicated ECG-LVH addition could improve the conventional model for predicting adverse outcomes within 4 years. These relationships persisted after excluding participants with cardiovascular disease history or taking antihypertension drugs or upon applying other ECG-LVH and Echo-LVH diagnostic criteria. Conclusion Our study provides strong evidence that ECG-LVH is associated with adverse outcomes, independent of Echo-LVH. Clinically, ECG-LVH could be considered as a consequential factor, especially in those with Echo-LVH. These findings have potential clinical relevance for risk stratification.

Background To investigate the relationship between triglyceride glucose-body mass index (TyG-BMI) and ischemic stroke. Methods Leveraging two Chinese general population surveys, the Northeast China Rural Cardiovascular Health Study (NCRCHS, N = 11,097) and the National Stroke Screening and Intervention Program in Liaoning (NSSIPL, N = 10,862), we evaluated the relationship between TyG-BMI and ischemic stroke by a restricted cubic spline and multivariate logistic regression after adjusting age, sex, level of education, exercise regularly, current smoking, current drinking, atrial fibrillation, hypertension, coronary artery disease, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The category-free analysis was used to determine whether TyG-BMI enhanced the capacity of estimating ischemic stroke. Results A total of 596 and 347 subjects, respectively, from NSSIPL and NCRCHS were survivors of ischemic stroke. In NSSIPL, the relationship between TyG-BMI and ischemic stroke was linear and did not have a threshold or saturation effect according to the results of the restricted cubic spline. The regression analysis indicated that the risk of ischemic stroke increased 20% for per SD increase of TyG-BMI after multivariate adjustment [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.10–1.32]. Compared with those in the lowest tertile, the risk of ischemic stroke in subjects with intermediate and high TyG-BMI was significantly higher [OR (95% CI): 1.39 (1.10–1.74); OR (95% CI) 1.72 (1.37–2.17), respectively]. Category-free analysis indicated that TyG-BMI had a remarkable improvement in the ability to estimate prevalent ischemic stroke [NRI (95% CI): 0.188 (0.105–0.270)]. These abovementioned relationships were confirmed in NCRCHS. Conclusions The present study found the robust correlation between TyG-BMI and ischemic stroke, independently of a host of conventional risk factors. Meanwhile, our findings also suggested the potential usefulness of TyG-BMI to improve the risk stratification of ischemic stroke.

Objectives To investigate the epidemiology of atrial fibrillation (AF) in postmenopausal women and to evaluate the association between age of menopause and AF. Study design A total of 9117 postmenopausal women were selected from a cross-sectional study conducted among the general population of north-east China from September 2017 and March 2019. Main outcome measures AF was diagnosed according to self-reported medical history of AF and/or current ECG findings. The epidemiology of AF including prevalence, awareness, use of anticoagulants and cardiovascular risk factors in postmenopausal women were carefully assessed. The association between age of menopause and AF was evaluated by stepwise logistic regression. Results The prevalence of AF was up to 1.1 % (95 % CI, 0.9 %–1.3 %) in postmenopausal women, but the awareness of it was 61.2 %. The proportion of AF patients requiring treatment with an oral anticoagulant (OAC) was as high as 87.8 % according to CHA2DS2-VASc score, while only 5.8 % of them received it. The prevalence of cardiovascular risks factors was high among postmenopausal women with AF, but awareness, treatment and control of these comorbidities were unacceptably low. Compared with the women with premature menopause ( Conclusions The widespread use of OAC and the control of cardiovascular risk factors in postmenopausal women with AF was of great significance in preventing AF-related stroke. The history of premature menopause provided a reliable opportunity for primary prevention of AF.

The aim of the present study was to compare the efficacy of microwave ablation (MWA) and surgical resection (RES) for the treatment of hepatocellular carcinoma (HCC) conforming to the Milan criteria and the associated short- and long-term survival rates. The baseline characteristics were obtained from 231 patients with HCC who met the Milan criteria. To compare the mortality rates between groups, survival analysis was conducted using the Kaplan-Meier method and the log-rank test. The factors associated with the survival rate were analyzed using Cox proportional hazard models. A total of 115 patients underwent RES, and 116 were treated with MWA. No significant differences were observed in the 1-, 3- and 5-year OS rates and the 1-year DFS rate between the two groups. The 7- and 10-year OS rates and the 3-, 5-, 7- and 10-year DFS rates of the RES group were significantly higher compared with those in the MWA group (P=0.004, P=0.002, P=0.003 and P=0.002, respectively). In addition, no marked differences were observed in the OS and DFS rates between the two groups of patients with solitary HCC lesions ≤3 cm (P=0.066 and P=0.056) and in the OS of those with solitary lesions of 3-5 cm (P=0.133); however the DFS of patients with single 3-5 cm HCC lesions in the RES group was notably higher compared with the MWA group (P=0.027). The Cox proportional hazard model revealed that age, hepatitis B and C virus infection, tumor size, number, platelet count and the type of treatment intervention were risk factors affecting the survival and recurrence in patients with HCC. These results suggested that RES may provide superior survival benefits compared with MWA for patients with HCC who meet the Milan criteria.

AIM To assess the impact of hepatitis B surface (HBsAg) seroclearance on survival outcomes in hepatitis B-related primary liver cancer. METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBsAg (-) and HBcAb (+) liver cancer were included in the HBsAg seroclearance (SC) group. HBsAg (+) liver cancer patients strictly matched for liver cancer stage (AJCC staging system, 8th edition), Child-Pugh score, and first diagnosis/treatment method (surgery, ablation and TACE) were assigned to the HBsAg non-seroclearance (NSC) group. Then, clinical, pathological and survival data in both groups were assessed. RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age (P < 0.001) and platelet count (P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma (ICC) and combined HCC-CC (CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups (4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group (P = 0.019), with 1-, 3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2% vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage I disease in the SC group was lower than that of the NSC group (P = 0.029). CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ-945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonst...

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood–brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(e-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

Objective. To investigate the relationship between the atherogenic index of plasma (AIP) and ischemic stroke. Design. We collected a range of data from 11,495 residents (aged ≥35 years; 54.28% female) residing in rural areas of northeast China between January and August 2013, including fasting lipid profile and anthropometric parameters. Logistic regression models were used to evaluate the correlation between AIP and ischemic stroke. Category-free analysis was used to determine whether AIP enhanced our capacity to estimate ischemic stroke. Results. Irrespective of gender, AIP was independently associated with the occurrence of ischemic stroke. The prevalence of ischemic stroke increased significantly from the lowest quartile to the highest quartile (females: 10.5%-48.7%, P < 0.001 ; males: 22.0%-36.5%, P = 0.08 ). After adjusting for age, gender, income, education, smoking, drinking, exercise, hypertension, body mass index (BMI), diabetes, atrial fibrillation, and a family history of stroke, we found that for every 1 standard deviation (SD) increase in AIP, there was a 34.8% and 20.9% increase in the prevalence of stroke for females and males, respectively. Curve fitting was also used to evaluate the linear relationship between AIP and the occurrence of ischemic stroke. Category-free analysis indicated that AIP significantly enhanced our ability to estimate ischemic stroke in both females (NRI (95% confidence interval (CI)): 0.188 (0.105-0.270)) and males (NRI (95% CI): 0.175 (0.017-0.333)). Conclusion. Analyses detected a significant and positive linear relationship between AIP and the prevalence of ischemic stroke. This relationship was independent of a range of conventional risk factors.

Background First-degree atrioventricular block (AVB) has traditionally been regarded as a benign condition but recent studies have challenged this conception. Prevalence of 1–2% have been reported in developed countries in Asia. However, no epidemiologic studies have established the prevalence of first-degree AVB in developing countries. The aim of the study was to investigate the prevalence of first-degree AVB in rural northeast China and identify the associated risk factors. Methods This cross-sectional study was undertaken from September 2017 to May 2018 in rural areas of Liaoning Province. It involved 10,926 participants aged ≥40 years (85.3% of those who were eligible). First-degree AVB was confirmed by at least two independent cardiologists. Risk factors were evaluated using stepwise logistic regression. Results The prevalence of first-degree AVB was 3.4% (95% confidence interval [CI]: 3.0–3.8%). Males had a higher prevalence than females (5.1% vs. 2.2%, p p p = 0.001), height (OR: 1.25; p = 0.008), systolic blood pressure (SBP) (OR: 1.15; p = 0.003), triglycerides (TG) (OR: 1.10; p < 0.001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.73; p < 0.001), heart rate (OR: 0.78; p < 0.001), and exercising regularly (OR: 0.73; p = 0.030) were independent risk factors. Conclusions First-degree AVB is highly prevalent in rural areas of northeast China. The associated independent risk factors include being male, older, and taller, higher SBP and TG, lower HDL-C and heart rate, and lack of exercise.

Background Stroke has become a major burden and public health problem in rural China. We aimed to comprehensively assess the current status of stroke burden as well as the associated risk factors in rural northeast China. Methods This population-based, cross-sectional study was conducted in 10,926 adults (response rate 85.3%) aged ≥40 years residing in rural northeast China. A multistage cluster sampling method was used to select the representative sample. The prevalent stroke cases were considered as stroke survivors on 31 August 2017. Stroke was diagnosed according to the World Health Organization’s recommendations and was classified as ischemic stroke and hemorrhagic stroke based on the results of computed tomography or magnetic resonance imaging. The status of related risk factors was also evaluated. Results Of the 10,926 participants, 731 were diagnosed with stroke (602 patients with ischemic stroke, 151 with hemorrhage stroke, and 22 with both ischemic stroke and hemorrhage stroke). The crude prevalence of overall stroke, ischemic stroke, and hemorrhage stroke was 6690.5, 5509.8, and 1382.0 per 100,000 people, respectively, and the age-standardized rate was 4903.8, 4041.7, and 990.9 per 100,000 people. Among the overall stroke population, 13.4% were living with consequences of stroke. Hypertension (86.7%), dyslipidemia (37.2%), and diabetes (24.5%) were highly prevalent in stroke participants. However, most of those comorbidities remained uncontrolled (93.7, 44.7, and 88.9%, respectively). Conclusion The burden of stroke in rural northeast China was substantial, with a high prevalence of stroke, recurrence, and disabilities. Uncontrolled comorbidities will likely contribute to recurrence and worsening disabilities in the coming decades. Strategies of long-term management of stroke and related risk factors are urgently required in rural northeast China.

ObjectiveTo evaluate the epidemiology of atrial fibrillation (AF) in northeast China.MethodsThis cross-sectional survey using a multistage, stratified and cluster random sampling method was conducted in Liaoning Province between September 2017 and March 2019. A total of 18 796 participants (28.9% urban, 71.1% rural) aged ≥40 years were included. All participants completed a questionnaire and underwent a physical examination and ECG. AF was diagnosed according to history and ECG findings.ResultsThe overall AF prevalence was 1.1%; it increased steeply with age. AF was more prevalent in men than in women (1.5% vs 0.9%, p2DS-VASc score, almost all (90.2%, 194/215) of our subjects required oral anticoagulant (OAC) therapy; however, only 4.1% actually received it. Moreover, hypertension (66.5%), dyslipidaemia (32.6%) and diabetes (24.2%) were highly prevalent in patients with AF, but their control rates were unacceptably low (7.0%, 8.6% and 28.8%, respectively).ConclusionsThe burden of AF in northeast China was substantial. Underuse of OAC therapy and uncontrolled comorbidities will likely contribute to the cardiovascular outcomes of patients with AF in the coming decades. Long-term management strategies for AF and related risk factors are required in northeast China.

Amplifying the chemotherapy-driven immunogenic cell death (ICD) for efficient and safe cancer chemoimmunotherapy remains a challenge. Here, a potential ICD nanoamplifier containing diselenide-bridged mesoporous organosilica nanoparticles (MONs) and chemotherapeutic ruthenium compound (KP1339) to achieve cancer chemoimmunotherapy is tailored. KP1339-loaded MONs show controlled drug release profiles via glutathione (GSH)-responsive competitive coordination and matrix degradation. High concentration of MONs selectively evoked reactive oxygen species production, GSH depletion, and endoplasmic reticulum stress in cancer cells, thus amplifying the ICD of KP1339 and boosting robust antitumor immunological responses. After the combination of PD-L1 checkpoint blockade, cancer cell membrane-cloaked KP1339-loaded MONs not only regress primary tumor growth with low systemic toxicity, but also inhibit distant tumor growth and pulmonary metastasis of breast cancer. The results have shown the potential of coordination and redox dual-responsive MONs boosting amplified ICD for cancer chemoimmunotherapy.

The inhibition of amyloid-β (Aβ) aggregation by photo-oxygenation has become an effective way of treating Alzheimer's disease (AD). New near-infrared (NIR) activated treatment agents, which not only possess high photo-oxygenation efficiency, but also show low biotoxicity, are urgently needed. Herein, for the first time, it is demonstrated that NIR activated black phosphorus (BP) could serve as an effective nontoxic photo-oxidant for amyloid-β peptide in vitro and in vivo. The nanoplatform BP@BTA (BTA: one of thioflavin-T derivatives) possesses high affinity to the Aβ peptide due to specific amyloid selectivity of BTA. Importantly, under NIR light, BP@BTA can significantly generate a high quantum yield of singlet oxygen (1 O2 ) to oxygenate Aβ, thereby resulting in inhibiting the aggregation and attenuating Aβ-induced cytotoxicity. In addition, BP could finally degrade into nontoxic phosphate, which guarantees the biosafety. Using transgenic Caenorhabditis elegans CL2006 as AD model, the results demonstrate that the 1 O2 -generation system could dramatically promote life-span extension of CL2006 strain by decreasing the neurotoxicity of Aβ.

Recently, photooxygenation of amyloid β (Aβ) has emerged as an effective way to inhibit Aβ aggregation in Alzheimer's disease (AD) treatment. However, their further application has been highly obstructed by self-aggregation, no metal chelating ability, and poor protein-enrichment capacity. Herein, porphyrinic metal-organic frameworks (PMOFs) are utilized as a superior CuII chelating and photooxidation agent for inhibiting Aβ aggregation. We selected only four classical kinds of POMFs (Zr-MOF, Al-MOF, Ni-MOF, Hf-MOF) for further investigation in our study, which are stable in physiological conditions and exhibit excellent biocompatibility. Among them, Hf-MOF was the most efficient Aβ photooxidant. A possible explanation about the difference in capacity of 1 O2 generation of these four PMOFs has been provided according to the experimental results and DFT calculations. Furthermore, Hf-MOFs are modified with Aβ-targeting peptide, LPFFD. This can not only enhance Hf-MOFs targeting cellular Aβ to decrease Aβ-induced cytotoxicity, but also improve Aβ photooxidation in the complicated living environment. More intriguingly, in vivo studies indicate that the well-designed LPFFD modified Hf-MOFs can decrease Aβ-induced neurotoxicity and extend the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Our work may open a new avenue for using MOFs as neurotoxic-metal-chelating and photo-therapeutic agents for AD treatment.

Over the past few decades, cancer nanomedicine has been under intensive development for applications in drug delivery, cancer therapy, and molecular imaging. However, there exist a series of complex biological barriers in the path of a nanomedicine from the site of administration to the site of action. These barriers considerably prevent a nanomedicine from reaching its targets in a sufficient concentration and thus severely limit its therapeutic benefits. According to the delivery process, these biological delivery barriers can be briefly summarized in the following order: blood circulation, tumor accumulation, tumor penetration, cellular internalization, and intracellular drug release. The therapeutic effect of a nanomedicine is strongly determined by its ability to overcome these barriers. However, advances in cancer biology have revealed that each barrier has its own distinct microenvironment, which imposes different requirements on the optimal design of nanocarriers, thus further complicating the delivery process. For example, the pH of blood is neutral, while the tumor extracellular environment features an acidic pH (pH

C60 has a special dual function; it can act as both a powerful reactive oxygen species (ROS) producer under UV or visible light and an ROS scavenger in the dark. However, ROS has double-edged effects in living systems. It is still a great challenge for biomedical application to switch and adjust the two opposite properties of C60 in one system. Herein, UCNP@C60 -pep (UCNP: upconversion nanoparticle, pep: Aβ-target peptide KLVFF) is designed as a near-infrared-switchable nanoplatform for synergy therapy of Alzheimer's disease (AD). Under near-infrared (NIR) light, the Aβ-targeting hybrid nanoparticles produce ROS and result in Aβ photooxygenation, which can hinder Aβ aggregation and mitigate the attendant cytotoxicity. In the dark, UCNP@C60 -pep shows protective effects against the increased oxidative stress. The ROS-generating and ROS-quenching abilities of UCNP@C60 -pep are both beneficial for decreasing Aβ-induced neurotoxicity and extending the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Moreover, UCNP@C60-pep can also be used for upconversion luminescence (UCL) and magnetic resonance imaging (MRI), which has benefits for "image-guided therapy." This study may offer a new perspective for the biological applications of C60 .

Non-human primates (NHPs) are confirmed as reservoirs of Cryptosporidium spp., Giardia intestinalis, and Enterocytozoon bieneusi. In this study, 197 fresh fecal samples from 8 NHP species in Qinling Mountains, northwestern China, were collected and examined using multilocus sequence typing (MLST) method. The results showed that 35 (17.8%) samples were positive for tested parasites, including Cryptosporidium spp. (3.0%), G. intestinalis (2.0%), and E. bieneusi (12.7%). Cryptosporidium spp. were detected in 6 fecal samples of Macaca mulatta, and were identified as C. parvum (n=1) and C. andersoni (n=5). Subtyping analysis showed Cryptosporidium spp. belonged to the C. andersoni MLST subtype (A4, A4, A4, and A1) and C. parvum 60 kDa glycoprotein (gp60) subtype IId A15G2R1. G. intestinalis assemblage E was detected in 3 M. mulatta and 1 Saimiri sciureus. Intra-variations were observed at the triose phosphate isomerase (tpi), beta giardin (bg), and glutamate dehydrogenase (gdh) loci, with 3, 1, and 2 new subtypes found in respective locus. E. bieneusi was found in Cercopithecus neglectus (25.0%), Papio hamadrayas (16.7%), M. mulatta (16.3%), S. sciureus (10%), and Rhinopithecus roxellana (9.5%), with 5 ribosomal internal transcribed spacer (ITS) genotypes: 2 known genotypes (D and BEB6) and 3 novel genotypes (MH, XH, and BSH). These findings indicated the presence of zoonotic potential of Cryptosporidium spp. and E. bieneusi in NHPs in Qinling Mountains. This is the first report of C. andersoni in NHPs. The present study provided basic information for control of cryptosporidiosis, giardiasis, and microsporidiosis in human and animals in this area.

Enterocytozoon bieneusi is an emerging and opportunistic enteric pathogen triggering diarrhea and enteric disease in humans and animals. Despite extensive research on this pathogen, the prevalence and genotypes of E. bieneusi infection in precious wild animals of giant and red pandas have not been reported. In the present study, 82 faecal specimens were collected from 46 giant pandas (Ailuropoda melanoleuca) and 36 red pandas (Ailurus fulgens) in the northwest of China. By PCR and sequencing of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene of E. bieneusi, an overall infection rate of 10.98% (9/82) was observed in pandas, with 8.70% (4/46) for giant pandas, and 13.89% (5/36) for red pandas. Two ITS genotypes were identified: the novel genotype I-like (n = 4) and genotype EbpC (n = 5). Multilocus sequence typing (MLST) employing three microsatellites (MS1, MS3 and MS7) and one minisatellite (MS4) showed that nine, six, six and nine positive products were amplified and sequenced successfully at four respective loci. A phylogenetic analysis based on a neighbor-joining tree of the ITS gene sequences of E. bieneusi indicated that the genotype EbpC fell into 1d of group 1 of zoonotic potential, and the novel genotype I-like was clustered into group 2. The present study firstly indicated the presence of E. bieneusi in giant and red pandas, and these results suggested that integrated strategies should be implemented to effectively protect pandas and humans from infecting E. bieneusi in China.

Survivin expression in the serum of patients with hepatocellular carcinoma (HCC) and nonmalignant chronic liver diseases remain to be elucidated. The aims of the present study were to evaluate the diagnostic role of survivin in the serum of patients with HCC and identify which ELISA kit performed best in detecting the levels of serum survivin. In total, 80 patients were included in the present study, including 20 patients with HCC, 20 patients with liver cirrhosis, 20 patients with chronic hepatitis B virus infection and 20 healthy volunteers. The levels of survivin protein in the serum were detected using two different ELISA kits (R&D and Abnova). The positive ratios of serum survivin detected by the R&D ELISA kit in all the cases were 8.75% (7/80; median, 0 pg/ml; range, 0–39.8 pg/ml) and in HCC patients were 5% (1/20; median, 0 pg/ml; range, 0–39.8 pg/ml). For the same samples analyzed using the Abnova ELISA kit, the positive ratios of serum survivin in all the cases were 22.5% (18/80; median, 0 pg/ml; range, 0–553.5 pg/ml) and in HCC patients were 25% (5/20; median, 0 pg/ml; range, 0–93.5 pg/ml). The results obtained by the different ELISA kits demonstrated no statistically significant differences in the level of survivin between HCC patients and healthy controls. The correlation coefficient was 0.0064 (P=0.481) when analyzing the same serum samples with the different ELISA kits. In addition, the highest positive ratio of serum survivin was observed using the Abnova kit. A statistically significant difference in the results was observed between the R&D and Abnova kits. In general, the levels and positive ratios of serum survivin in the patients with HCC were significantly low. Furthermore, no difference was observed between HCC patients and controls in regard to the levels of serum survivin detected by the R&D and Abnova ELISA kits. In conclusion, survivin is unlikely to be a promising serological maker for the diagnosis of HCC.

Background and Aim To compare the efficacy of microwave ablation (MWA) and surgical resection (RES) in the treatment of hepatocellular carcinoma (HCC) conforming to Milan criteria. Methods Two hundred twenty-four patients met the inclusion criteria and were enrolled in the study. One hundred and seventeen patients received MWA, and 107 patients underwent RES. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results The 1-, 3-, and 5-year OS rates were 94%, 70%, 52% for the MWA group and 94%, 72%, 60% for the RES group (P = 0.513). The corresponding DFS rates for the two groups were 77%, 38%, 18% and 85%, 57%, 31% (P = 0.005). In subgroup analyses of patients with solitary HCC ≤ 3 cm, there were no significant differences in OS rates and DFS rates between the two groups (P = 0.577 and P = 0.140). For patients with solitary HCC 3 to 5 cm, there was no significant differences in OS rates between the two groups (P = 0.820), the DFS rates was significantly higher in the RES group than in the MWA group (P = 0.014). Conclusions MWA results in lower DFS rates than RES for HCC conforming to Milan criteria. However, the OS rates are comparable between the two therapies. For solitary HCC ≤ 3 cm, MWA is as effective as RES.

Background and Aim Recent studies have shown that imbalance between tumor-infiltrating interleukin (IL)-17+ T cells and regulatory T cells (Tregs) is an important regulator of progression in various cancers, but little is known regarding this imbalance in hepatocellular carcinoma (HCC). This study explored the role of imbalance between IL-17+ T cells and Tregs in the immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection. Methods Fifty-six of patient-matched tumors and peritumoral surgical specimens from 56 patient with HCC and 136 liver biopsies specimens from 46 patients with CHB, 37 with atypical hyperplasia (AH), and 53 with HCC were enrolled. The expressions of IL-17, FoxP3, CD4, and CD8 in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. Results The density of liver infiltrated FoxP3+ Tregs was increased in a stepwise manner from CHB to AH then HCC, while there was a decreasing trend for the density of IL-17+ T cells and CD8+ T cells. In surgical specimens of less differentiated HCC, the quantity of tumor-infiltrating FoxP3+ Tregs was significantly lower and IL-17+ T cells and CD8+ T cells were significantly higher. Additionally, peritumoral IL-17+ T cells were increased in poorly differentiated HCC. High intratumoral FoxP3+ Tregs with high intratumoral IL-17+ T cells showed a significantly lower overall survival (OS) and disease-free survival (DFS) compared with other groups (OS, P = 0.033; DFS, P = 0.004). High intratumoral FoxP3+ Tregs with high peritumoral IL-17+ T cells showed a significantly lower survival rate compared with other groups (OS, P

In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC.

Objective To evaluate the therapeutic effect and safety of time-oriented points opening of Linggui Bafa for Bell's palsy and provide a new idea for the clinical treatment of this problem. Methods Fifty-four cases included in the study were randomized into two groups, and the treatment group was treated with the routine acupuncture combined with time-oriented points opening of Linggui Bafa. The control group was treated with the routine acupuncture only, Hegu ( LI 4), Kūnlun ( BL 60), Jiachē ( ST 6), Dicāng ( ST 4), Xiaguān ( ST 7), Cuanzhu ( BL 2), Yangbai ( GB 14), and Quanliao ( SI 18) were selected as the main points. The manipulation and time of retaining needles were as same as the treatment group. Both groups were treated once a day, 5 days made one session and 4 sessions were required in all. Modified Portmann's scale, Horse-Brackmann grading scale (H-B), FDIP and FDIS were used to assess the therapeutic effect after the treatment. Results The curative and improvement rate in the treatment group was 80.8% (22/26), and that in the control group was 66.7% (16/24), with the statistically significant difference ( P P Conclusion The method of time-oriented points opening of Linggui Bafa for Bell's palsy is better than the routine acupuncture for Bell's palsy.

Aim Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters. Methods Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay. Results GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P

Astilbin, a flavonoid compound, was isolated from the rhizome ofSmilax glabraRoxb. (with red cross-section) grown in Guizhou Province, China. We accessed its effect and potential mechanism on attenuation of the inflammatory response in CFA-induced AA rats. Our results showed that daily oral administration of astilbin at 5.3 mg/kg reduced joint damage in the hind paw of AA rats. Accordingly, astilbin exhibited remarkable inhibitory effects on TNF-α, IL-1β, and IL-6 mRNA expression. Significant decrease of serum cytokine levels of TNF-α, IL-1β, and IL-6 was also observed in astilbin-treated AA rats compared to the vehicle-treated AA rats. The reduced expression of these cytokines was associated with protein activity suppression of three key molecular targets in the pathogenesis of RA, including IKKβ, NF-κB p65 subunit, and TLR adaptor MyD88. Furthermore, the therapeutic effects of astilbin on the inhibition of cytokines production as well as the reduction of inflammatory response in AA rats are close to a commonly used antirheumatic drug, leflunomide. Collectively, our data suggest that the action mechanism of astilbin, as an anti-inflammatory agent for RA treatment, is associated with modulating the production of proinflammatory cytokines and inhibiting the expression of key elements in NF-κB signaling pathway mediated by TLR.

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare hereditary sensory autonomic neuropathy. Anesthetic management of those patients is challenging for anesthesiologist because of the potential risks for them including regurgitation and aspiration, sympathetic nervous dysfunction, mandibular osteomyelitis as well as hyperthermic events. Case report: We present total intravenous anesthesia (TIVA) with spontaneous respiration via facemask was applied in a 2 y old child with CIPA who underwent closed reduction and plaster external fixation of a bilateral dislocation of the hip. The patient vital signs remained stable, and did not show any signs of distress by anesthetics during the surgery. And no complication occurred. Conclusion: TIVA with spontaneous respiration via facemask is an effective and safe anesthetic management for patients with CIPA.

This study aimed to assess whether maifanite can improve the learning and memory, and antioxidant abilities of Alzheimer's disease (AD) rats. The 70 rats were divided into seven groups: [A] normal control group, [B] AD model group, [C] sham group, [D] positive control group (donepezil), [E] low-dose maifanite group, [F] middle-dose maifanite group, [G] high-dose maifanite group. For [B], [D], [E], [F], and [G] groups, Aβ(25-35) ventricle injection was carried out, then respective medicine were administered once a day for 60 consecutive days. The step-down and step-through test were used to measure learning and memory ability. The hippocampus levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were assayed. The hippocampus contents of Al, Fe, Cu, Zn, Se, and Mn were analyzed by inductively coupled plasma-atomic emission spectrometer. Maifanite decreased the acquisition errors and the retention errors while prolonging the step-down latency, and decreased the number of electric shocks while prolonging the first latency of AD rats. Aβ(25-35) ventricle injection initiated the decrease of SOD and GSH-Px activities and the increase of MDA content, and triggered the rise of Al, Fe, and Cu levels and the decline of Mn, Zn, and Se levels. The SOD and GSH-Px activities were enhanced followed by reduced MDA level, and the levels of Mn, Zn, and Se increased accompanied by Al, Fe, and Cu decreased in the maifanite treat groups. Maifanite could improve the learning and memory, and the antioxidant abilities of AD rats. Maifanite had the potential prevention and treatment for AD.

The diagnostic value of combining glypican-3 (GPC3) and CD34 staining for small nodules in liver biopsy specimens has not been evaluated. In this study, 201 thin-core biopsy specimens were assessed using GPC3 and CD34 immunochemical staining, including 33 cirrhotic regenerative nodules, 31 high-grade dysplastic nodules, 70 hepatocellular carcinomas (HCCs) with nodules 3 cm or smaller, and 67 HCCs with nodules larger than 3 cm. The results showed that the accuracy of GPC3 staining (90.3%) among liver nodules 3 cm or smaller was better than its use among all nodules (P = .045). Furthermore, the positive expression rate of costaining was significantly greater than that observed for GPC3 or CD34 single staining (P < .001 and P = .002, respectively).These data demonstrate that GPC3 staining is more accurate for the diagnosis of HCC on thin-core biopsy specimens in nodules 3 cm or smaller compared with its use in all nodules, while GPC3 and CD34 costaining has better diagnostic value than does single staining.

Astilbin, a flavonoid compound, was isolated from the rhizome of

Objective This study was aimed to identify the specific methylation profile in bile specimens of pancreaticobillary diseases for differential diagnosis of malignant biliary stricture. Design and methods In a total of 80 bile specimens from pancreaticobillary diseases, the methylation status of 19 tumor suppressor genes were analyzed by methylation-specific PCR and the methylation index (MI) were compared between the malignant and benign groups. Results Methylation of DKK3, p16, SFRP2, DKK2, NPTX2 and ppENK were more frequently detected in the bile of malignant biliary strictures than benign patients. When setting MI 0.5 as the threshold, this 6-gene panel could distinguish the malignant biliary stricture with a high sensitivity, specificity and accuracy (77.27%, 77.78% and 77.50%, respectively). Conclusion The methylation profile including 6 specific genes in bile may be a promising biomarker for differential diagnosis between malignant and benign biliary strictures.

Field cancerization currently described the theory of tumorigenesis and, until now, has been described in almost all organ systems except in liver. For this reason, we explore the presence of field cancerization in liver and its underlying clinical implication in hepatocellular carcinoma (HCC). In our study, methylation profile of HCC and surgically resected margin (SRM) were established by methylation-specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal liver were treated in the same way as the background control. The correlation analysis among the methylation profile of HCC, SRM and clinicopathological data of HCC patients was made respectively. Our results showed that methylation abnormities related to HCC, but not background disease existed in histologically negative SRM. Monoclonal and polyclonal models may coexist in field cancerization in liver. Patients with RIZ1 methylation in SRM had a shorter disease free survival. The local recurrence trend of early and later recurrence in HCC is potentially related to a second field tumor. From these results, we can suggest that field cancerization exists in liver. The study of field cancerization in liver plays an important role in hepatocarcinogenesis. Second field tumor derived form field cancerization may have important implications in HCC prognosis assessment that is worthy of further study.

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.