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The current study aimed to investigate the role and underlying mechanism of Resolvin D1 (RvD1) alleviating spinal nerve ligation (SNL)-induced neuropathic pain (NP) and its interplay with regulatory cascades of Nod-like Receptor Protein 3 (NLRP3) inflammasome. Sprague-Dawley male rat models of SNL-stimulated NP were established, which were pre-treated with different doses of RvD1, WRW4 (ALX/FPR2 inhibitor) or U0126 (ERK inhibitor) for three successive days following the operation. Pain behavior was assessed by measuring changes in the mechanical sensitivity of the hind paws during an observation period of seven consecutive days. The spinal cord (SC) and dorsal root ganglions (DRGs) tissues were collected on postoperative day 7. Immunohistochemistry (IHC) and Western blot were performed to determine the expression levels of NLRP3 inflammasome complex, ALX/FPR2 receptor and extracellular signal-related kinase (ERK). The pro-inflammatory mediators (IL-1β and IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that RvD1 could alleviate mechanical allodynia significantly in the SNL-induced NP rat models. Also, RvD1 inhibited the expression of p-ERK, the NLRP3 inflammasomes complex and its corresponding downstream pro-inflammatory mediators which were significantly enhanced in the SC and DRGs of the rat SNL models. While these changes were partially reversed by pre-administration of WRW4 and further strengthened by co-treated with U0126. Our results suggest that RvD1 dependent on ALX/FPR2 may have an analgesic and anti-inflammatory influence on SNL-induced NP driven by inhibiting NLRP3 inflammasome via ERK signaling pathway. These data also provide strong support for the recent modulation of neuro-inflammatory priming and highlight the potential for specialized pro-resolving mediators (SPMs) as novel therapeutic avenues for NP.

Thomas Bradbury,1 Gian Luca Di Tanna,1 Anish Scaria,1 Allison Martin,1 Fu-Qiang Wen,2 Nan-Shan Zhong,3 Jin-Ping Zheng,3 Peter J Barnes,4 Bartolome Celli,5 Norbert Berend,1 Christine R Jenkins1 On behalf of the TASCS Investigators1Respiratory Group, The George Institute for Global Health, Sydney, NSW 2042, Australia; 2West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4National Heart & Lung Institute, Imperial College, London, UK; 5Pulmonary and Critical Care Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Thomas BradburyRespiratory Group, The George Institute for Global Health, Level 5, 1 King St, Newtown, Sydney, NSW 2042, Australia, Tel +61 2 8052 4413, Email tbradbury@georgeinstitute.org.auBackground and Objectives: The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention.Methods: This was a post-hoc analysis of the TASCS dataset – a double-blinded, placebo-controlled trial conducted in patients with moderate–severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥ 300 eosinophils/μL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate.Results: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (± 8) years and a predicted forced expiratory volume in 1s (FEV1) of 43% (± 16). The annualized moderate–severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06– 1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George’s Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups.Conclusion: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥ 300 cells/μL compared to placebo.Keywords: eosinophil, COPD, clinical trial, China, theophylline, prednisone

To explore the clinical efficacy of focused extracorporeal shock wave therapy with centrifugal exercise in the treatment of greater trochanteric pain syndrome.From September 2017 to June 2019, 53 eligible cases of greater trochanteric pain syndrome were randomly divided into observation group (29 cases) and control group (24 cases). In observation group, there were 8 males and 21 females, aged from 38 to 62 years old with an average of (49.96±6.39) years old; the course of disease ranged from 6 to 13 months with an average of (8.58±1.99) months;treated with focused extracorporeal shock wave therapy with centrifugal exercise. In control group, there were 5 males and 19 females, aged from 39 to 62 years old with an average of (52.79±5.86) years old;the course of disease ranged from 6 to 14 months with an average of (9.04±2.51) months;treated with centrifugal exercise alone. Visual analogue scale (VAS) and hip Harris score were measured before ESWT treatment and at 1, 2, and 6 months to evaluate relieve degree of pain and functional recovery of hip joint, respectively.At 1 month after treatment, there were no significant differences in VAS, hip Harris score and treatment success rate (allIn treatment of greater trochanteric pain syndrome, focused extracorporeal shock wave therapy with centrifugal exercise could significantly relieve symptoms of lateral hip pain, improve functional recovery of hip joint with good safety. This treatment strategy is worthy of application and promotion in clinical practice.

Fumonisin B1 (FB1) is a harmful environmental pollutant that induces hepatotoxicity, but the mechanism is still poorly understood. Therefore, the aim of this work was to investigate the effects of FB1 on the liver of mice and discover the underlying molecular mechanisms. A total of 40 male mice were exposed to 0 or 5 mg/kg FB1 for 42 days, and then, they were sacrificed, and the liver and blood were collected. Besides, AML12 cells were exposed to FB1. Biochemical and liver related indexes as well morphological changes, redox, apoptosis and fibrosis related markers were measured in liver and AML12 cells. The results showed that the liver function and biochemical indexes in the blood were changes, and the histopathological analysis indicated that FB1 exposure caused hepatic sinusoid atrophy, hemosiderosis, hepatocyte steatosis and fibrosis, finally inducing liver injury. Notably, a significant increase in the intracellular antioxidant enzymes SOD1, SOD2, NF-κB (p65), H

To investigate the clinical and pathological characteristics in patients with pulmonary inflammatory pseudotumors (PIP). This retrospective study included 31 patients with PIP from 2001 to 2019. Preoperative computed tomography scan was performed in all patients. Clinical and pathological characteristics were collected and analyzed. Thirty-one patients (16 female and 15 male) were recruited, with a median age of 57 years (range, 11–72 years). Eight (25.8%) patients were asymptomatic, and the others had symptoms characterized by cough with sputum, chest and back pain, dry cough, fever and blood in sputum, or hemoptysis. All cases were single lesions, including 23 cases in the right lung, and 8 cases in the left lung. Computed tomography scan demonstrated irregular lobulated nodules or masses in 14 patients, and regular round or oval nodules or masses in 11 cases. The blurred edge of tumors and spiculation was found in 12 cases. Microscopic results were characterized by the collection of inflammatory mesenchymal cells. Immunohistochemical examination showed vimentin, smooth muscle actin, and anaplastic lymphoma kinase positive. Complete tumor resection was obtained in all cases. No recurrence or metastasis was observed during the follow-up period. PIP has a variety of manifestations. Preoperative diagnosis is difficult to reach. The final diagnosis still depends on the pathological and immunohistochemical examination. Complete surgical resection is the main treatment at present, and the overall prognosis is good.

Background The efficacy of core decompression plus autologous bone mesenchymal stem cells (BMSCs) for the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to explore the efficacy of core decompression combined with BMSCs for OFNH patients. Methods We searched PubMed, Embase, Web of Science, and the Cochrane library databases through October 2018 for randomized controlled trials (RCTs) assessing the effect of core decompression combined with BMSCs for OFNH patients. The primary outcome was the visual analog scale (VAS) score at 6 months, 12 months and 24 months. The pooled data were analyzed using Stata 12.0 software. Results Fourteen studies with 540 patients (core decompression + BMSCs = 275, core decompression alone = 265) were included in our meta-analysis. Compared with the core decompression alone group, the core decompression + BMSCs group showed a significant decrease in the VAS score at 6 months, 12 months and 24 months, and a decrease in the number of hips undergoing total hip arthroplasty (THA), the Western Ontario and McMaster Universities (WOMAC) score and the volume of the postoperative necrotic zone. Core decompression + autologous BMSCs was associated with an increase in HHS postoperatively. No significant difference existed in adverse events. Conclusions Compared with core decompression alone in the treatment of ONFH, the combined utilization of core decompression and autologous BMSCs has better pain relief and clinical outcomes and can delay the collapse of the femoral head more effectively.

A germacrane sesquiterpenoid library containing 30 compounds (2-31) was constructed by structural modification of a major component aristolactone (1) from the traditional Chinese medicine Aristolochia yunnanensis. Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor β 1 (TGFβ1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFβ/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFβ type I receptor (IC50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.

Limb ischemia reperfusion (LIRI) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. Calcium overloading and inflammation are considered to be two of the pathological mechanisms of limb ischemia/reperfusion (I/R) injury. Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine with a powerful anti-inflammatory properties. We studied the probable restorative effect of THSWD on limb I/R-induced calcium overloading and inflammation in myoblast obtained from gastrocnemius muscle tissues of Sprague-Dawley rats (Frizzled Z5,a wnt5a blocker; KN-93, a calmodulin-dependent protein kinase II (CamkII) blocker; XeC, a IP3R blocker as positive controls). The simulated ischemia and reperfusion(I/R) solutions were used to imitate LIRI environment. The results showed that after I/R treatment, the secretion of proinflammatory factors (TNF-α and IL-1β) and Wnt5a/Ca2+ signal molecules (wnt5a, camkII, and IP3R) upregulated significantly, the Ca2+ concentration enhanced too in myoblast cells. THSWD pretreatment decreased the secretion of TNF-α and IL-1β, Ca2+ concentration; and abated the Wnt5a/Ca2+ signal molecules of wnt5a, camkII and IP3R expression activated by I/R injury; but could not abated the Wnt11 and protein kinase C (PKC) expression significantly, the results was similar with Frizzled Z5 treatment cells. Our research illustrated that THSWD may have a mitigating effect on LIRI targeting Wnt/IP3R/CAMKII but not Wnt/IP3R/PKC signaling pathway for the first time. This study may encourage the use of THSWD in the critical clinical settings with LIRI.

Genes in the S100 family are abnormally expressed in a variety of tumor cells and are associated with clinical pathology, but their prognostic value in melanoma patients has not yet been fully elucidated. In this study, we extracted and profiled S100 family mRNA expression data and corresponding clinical data from the Gene Expression Omnibus database to analyze how expression of these genes correlates with clinical pathology. Compared with normal skin, S100A1, S100A13, and S100B were expressed at significantly higher levels in melanoma samples. S100A2, S100A7, S100A8, S100A9, S100A10, S100A11, and S100P were all highly expressed in primary melanoma samples but were expressed at low levels in metastatic melanoma, and all of these genes were strongly correlated with each other (P

Background/Aims: In heart failure patients with high prevalence of chronic renal disease (CKD), hospitalization and mortality, whether the lipid profile was associated with renal dysfunction remained unknown. The present study intended to clarify the association between the lipid profile and renal dysfunction in the heart failure patients. Methods: 336 hospitalized heart failure patients with left ventricle ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. The estimated glomerular filtration rate (eGFR) < 90 mL/min·1.73 m2 was defined as renal dysfunction. The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with eGFR. The significantly correlated factors were enrolled in Logistic regression as confounding factors to determine the association between the lipid profile and renal dysfunction in the heart failure patients. Results: 182 patients (54.2%) had renal dysfunction and 154 patients (45.8%) did not have renal dysfunction. The waist circumference, platelet counts, platelet distribution width (PDW), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1), albumin and left ventricular ejection fraction (LVEF) are positively correlated with eGFR (all P< 0.05). Meanwhile, the age, mean platelet volume (MPV), neutrophilic granulocyte percentage (NEUT%), urea nitrogen (BUN), creatinine and total bilirubin (TBIL) are negatively correlated with eGFR (all P< 0.05). The total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) show no correlation with eGFR. After the adjustment of sex, hypertension, diabetes mellitus, age, waist circumference, platelet counts, MPV, PDW, NEUT%, TBIL, albumin and LVEF, HDL-C is the only lipid factor still significantly associated with renal dysfunction in hospitalized heart failure patients (OR=0.119, P=0.003). Conclusion: Among the lipid profile of TC, triglyceride, LDL-C, HDL-C, apo A1 and apo B, the HDL-C is the only lipid factor significantly associated with renal dysfunction in hospitalized heart failure patients.

Background Locally advanced rectal neuroendocrine neoplasms (NENs) are rare, and the therapeutic effects of surgery in improving the prognosis have been questioned in previous reports. Materials and methods The research included 58 consecutive patients with locally advanced rectal NENs from three Chinese medical centers between 2000 and 2020. All have received radical surgical treatment. The clinicopathological and survival data were collected. Kaplan-Meier methods and a Cox proportional hazards regression model were used to evaluate the prognosis and identify independent prognostic factors. Results All patients were followed up for a median period of 36 (2–125) months. Of the 58 patients, 13 (22.4%) had G1 neuroendocrine tumors (NETs), 15 (25.9%) had G2 NETs, 6 (10.3%) had G3 NETs, and the remaining 24 (41.4%) patients had G3 neuroendocrine carcinomas (NECs). The 1-year and 3-year disease-free survival (DFS) rates were 64.5% and 48.8%, respectively. The 1-year and 3-year overall survival (OS) rates were 90.5% and 75.4%, respectively. Univariate analysis demonstrated that tumor differentiation (p = 0.002), gross morphology (p = 0.009), T stage (p = 0.024), and extramural vascular invasion (p = 0.009) were associated with the OS. The subsequent multivariate analysis confirmed that tumor differentiation [hazard ratio (HR) = 6.002, 95% confidence interval (CI): 1.210–29.767, p = 0.028] and gross morphology (HR = 3.438, 95% CI: 1.038–11.382, p = 0.043) were independent prognostic factors affecting the clinical outcomes. Conclusions Rectal NENs are a heterogeneous group of diseases. The survival benefits obtained from surgery vary widely based on the tumor clinicopathological features. Patients with G3 NECs and ulcerative mass are at high risks of poor prognosis.

To investigate the clinical efficacy and advantage of minimally invasive transforaminal lumbar interbody fusion under microscope-assisted Zista channel in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis.The clinical data of 18 patients with degenerative lumbar spondylolisthesis treated by microscope-assisted Zista channel MIS-TLIF operation from January 2017 to March 2018 were analyzed retrospectively. There were 10 males and 8 females with an average age of 59 years (48 to 70). The course of spondylolisthesis ranged from 6 months to 5 years with an average of 33 months. The segment of spondylolisthesis was LAll the patients completed the operation successfully and were followed up more than 12 months after operation. Operation time was(160.45±34.98) min, intraoperative blood loss was (88.32±21.12) ml, postoperative drainage volume was (50.34 ±18.22)ml, and walking time after operation was (20.65±6.25) h. Preoperative and postoperative at 7 days, 3 months, 12 months, VAS score of low back pain was 7.81±2.16, 4.19±1.17, 2.25±0.62 and 1.53±0.58 respectively, VAS score of leg pain was 8.47± 2.21, 3.45±0.86, 2.31±0.73 and 1.43±0.47, JOA score was 12.01±2.33, 18.56±3.12, 23.54±3.31 and 26.34±2.65. There were significant differences in VAS and JOA scores between preoperative and postoperative (MIS-TLIF under microscope-assisted Zista channel has obvious minimally invasive advantages in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis, and it is a safe and effective method.

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.

Studies have shown that acupuncture is very effective in treating chronic stress depression. However, little is known about the therapeutic mechanism of electro-acupuncture. Metabolomics, on the other hand, is a technology that determines the metabolic changes of organisms caused by various interventions as a whole and is related to the overall effect of electro-acupuncture (EA). 1HNMR, serum sample analysis, and histopathology and molecular biology analysis were used to evaluate the effects of EA. The results show that electro-acupuncture points can regulate the heat pain threshold of chronic stress model rats and change the morphology of adrenal cortex cells Structure, and regulate the contents of corticotropin-releasing hormone, Corticosterone (CORT), glucose, alanine and valine in the samples. These findings help to clarify the therapeutic mechanism of electro-acupuncture on heterologous chronic stress model rats. The effect of electro-acupuncture on improving chronic stress is likely to be achieved by regulating glucose metabolism, which can provide a reference for clinical acupuncture treatment of chronic stress depression.

To investigate the clinical efficacy and advantages of the full endoscopic I See technique for the single-segment degenerative lumbar spinal stenosis.The clinical data of 38 patients with the single-segment degenerative lumbar spinal stenosis treated by full endoscopic I See technique from January 2017 to March 2018 were analyzed retrospectively. There were 16 males and 22 females, aged from 35 to 79 years with an average of(53.45±12.56) years. Five cases were LAll the patients were followed up for more than 12 months after operation. The length of operation was from 55 to130 (86.0± 17.5) min. Intraoperative blood loss was ranging from 10 to 50 (17±6) ml, and the hospitalization length was from 3 to 7 days with an average of 4.6 days. The VAS scores of low back pain assessed before operation, and 3 d, 3 months, 12 months post operation were 6.67 ±1.25, 3.87 ±1.35, 2.55 ±1.21, 2.05 ±0.97, respectively, and the differences were statistically significant (P0.05);VAS scores of leg pain at these time points were 7.85±2.62, 3.31±1.42, 2.02±1.13, 1.85±0.86, respectively, and the differences were statistically significant (Full endoscopic I See technique is effective in the treatment of single-segment degenerative lumbar spinal stenosis, with the advantages of less trauma, shorter hospital stay, and faster recovery.

This study aims to estimate the effective doses of dental X-ray devices under common scanning protocols. After putting TLDs in the Alderson Radiation Therapy Phantom, we exposed the phantom under common scanning protocols of three dental X-ray devices, namely CBCT, dental panoramic machine and intraoral round cone device. Then effective doses were calculated using the measured absorbed doses of organs and tissues. Tissue weighting factors recommended by the ICRP were adopted in the calculation. Effective doses under common scanning protocols of three Dental X-ray devices were obtained. The effective dose of dental CT was 0.20 mSv, and that of dental panoramic machine and intraoral radiography were 0.013 and 0.0050 mSv, respectively. The tissue absorbed doses of dental CT scan were 0.63 mGy of brain, 7.7 mGy of salivary glands, 8.7 mGy of thyroid and 4.0 mGy of the lens of the eye. The tissue absorbed doses from dental panoramic machine are 0.62 mGy of salivary glands and 0.25 mGy of thyroid. And finally the tissue absorbed dose of intraoral radiography was 0.80 mGy of salivary gland. Among the three dental X-ray devices studied, dental CBCT scan can cause much higher effective dose than the other two. Brain, salivary glands, thyroid and the lens of the eye are tissues receiving relatively higher absorbed doses.

Objective: Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma. Methods: A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection. Results: Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS. Conclusion: Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC. Advances in knowledge: We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.

Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Plant-extracted flavonoid glycosides have been suggested to be bioactive compounds with pleiotropic functions, such as anti-cancer, anti-inflammatory, antioxidant and effects. Our study was attempted to explore the anti-cancer role of linarin (acacetin-7-O-β-d-rutinoside) in glioma in vitro and in vivo. Nuclear factor kappa-B (NF-κB) activity is a common phenomenon in various cancers, resulting in abnormal cell proliferation, malignant transformation, or resistance to cell death. P53, an essential tumor suppressor, plays an important role in preventing tumor progression. Our data indicated that linarin suppressed glioma cell proliferation and migration by inducing apoptosis, which was through reducing cell cycle-related signals, including Survivin, p-Rb, and Cyclin D1, while promoting p21, Bax, Caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Also, we found that linarin-reduced cellular proliferation of glioma was dependent on p53 up-regulation and Nuclear factor kappa-B (NF-κB)/p65-down-regulation, thereby inhibiting glioma cell growth. We further conformed the inhibitory effect of linarin in vivo using xenograft tumor model. Linarin significantly triggered apoptosis as well as the tumor growth in animals, accompanied with p53 increase and p65 decrease. Our data illustrated that linarin could be used as a promising candidate against glioma progression.

Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population. Among the 11 polymorphisms, only CASP8 rs3834129 (−652 6N ins/del) modified HCC risk. Compared with CASP8 −652 insins genotype, the deldel (adjusted OR 0.717, 95% CI 0.553–0.930) and insdel (adjusted OR 0.731, 95% CI 0.554–0.964) genotypes had a significantly decreased HCC risk. Furthermore, this polymorphism was significantly associated with decreased portal vein tumor thrombosis (adjusted OR 0.554; P = 0.044) and reduced postoperative recurrence (adjusted OR 0.356; P

Objective: This study was designed to compare the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma (HCC). Methods: From March 2015 to August 2015, a total of 44 patients with moderate and advanced HCC, who were admitted in the Navy General Hospital of China, were included into this study. These patients were randomly divided into 2 groups: group A and group B. Patients in group A underwent TACE alone, while patients in group B underwent the combined treatment of TACE with apatinib. Differences in preoperative general data between these 2 groups were not statistically significant (P > 0.05). All patients were followed up for 12–18 months. Changes in α-fetal protein (AFP) at 3 months after treatment and the objective response rate (ORR) at 3, 6, 9 and 12 months after treatment were compared between these 2 groups. Furthermore, progression-free survival (PFS) and the incidence of adverse reactions were also compared between these 2 groups. Results: AFP levels in groups A and B significantly decreased after 3 months of treatment, compared with the levels before treatment, and the differences were statistically significant (P < 0.05). However, at 3 months after treatment, the difference between these 2 groups was not statistically significant (P > 0.05). ORR at 3, 6, 9 and 12 months after treatment was 36.36%, 27.27%, 13.64% and 9.09%, respectively, in group A; and 60%, 50%, 45% and 35%, respectively, in group B. At 3 and 6 months after treatment, the differences between these 2 groups were not statistically significant (P > 0.05); while at 9 and 12 months after treatment, the differences between these 2 groups were statistically significant (P < 0.05). The median PFS was 6.0 months in group A and 12.5 months in group B, and the difference was statistically significant (P < 0.05). The incidences of complications were related to oral apatinib, such as hypertension, hand-foot syndrome and proteinuria, were higher in group B than in group A, and the differences were statistically significant (P < 0.05). These symptoms all alleviated after symptomatic treatments. Conclusions: For intermediate and advanced HCC, the long-term curative effect of TACE combined with apatinib is better than that of TACE alone. The former can obviously prolong the PFS of patients and has a confirmed safety.

Objective To our knowledge, the independent association between central obesity, defined by waist circumference (WC) or waist-to-hip ratio (WHR), and diabetic retinopathy (DR) remains unknown in Chinese individuals. Method The study was conducted in two stages. First, the relationship between WC or WHR and DR was estimated in a case-control set (DR vs. non-DR) for the whole population before and after propensity score matching. Subsequently, a systematic review and meta-analysis was performed on evidence from the literature to validate the relationship. Results Of 511 eligible patients, DR (N = 156) and non-DR (N = 156) patients with similar propensity scores were included in the propensity score matching analyses. Central obesity (defined by WC) was associated with risk of DR (odds ratio [OR] 1.07, 95% confidence interval [95% CI] (1.03–1.10). The meta-analysis showed that central obesity significantly increased the risk of DR by 12% (OR 1.12, 95% CI 1.02–1.22). Analysis of data from 18 studies showed a significant association between continuous body mass index and risk of proliferative DR (OR 0.95, 95% CI 0.93–0.98; I2 = 50%). Conclusion Central obesity, particularly as defined by WC, is associated with the risk of DR in the Chinese population.

Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long‐acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat‐to‐mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

Background Colorectal high-grade neuroendocrine neoplasms (HGNENs) are rare and constitute less than 1% of all colorectal malignancies. Based on their morphological differentiation and proliferation identity, these neoplasms present heterogeneous clinicopathologic features. Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial. Aim To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy. Methods This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019. The clinicopathologic characteristics and follow-up data were carefully collected from their medical records, outpatient reexaminations, and telephone interviews. A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease. Results According to the latest recommendations for the classification and nomenclature of colorectal HGNENs, 61 (84.7%) patients in our cohort had poorly differentiated neoplasms, which were categorized as high-grade neuroendocrine carcinomas (HGNECs), and the remaining 11 (15.3%) patients had well differentiated neoplasms, which were categorized as high-grade neuroendocrine tumors (HGNETs). Most of the neoplasms (63.9%) were located at the rectum. More than half of the patients (51.4%) presented with distant metastasis at the date of diagnosis. All patients were followed for a median duration of 15.5 mo. In the entire cohort, the median survival time was 31 mo, and the 3-year and 5-year survival rates were 44.3% and 36.3%, respectively. Both the univariate and multivariate analyses demonstrated that increasing age, HGNEC type, and distant metastasis were risk factors for poor clinical outcomes. Conclusion Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes. However, patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.

Rationale: Paraganglioma refers to a set of neuroendocrine tumors derived from the chromaffin cells of the adrenal diplomatic ganglion. Paragangliomas can be classified as functional or nonfunctional based on the ability to synthesize and release catecholamines. Patient concerns: We report a 47-year-old man with a functional paraganglioma in the left posterior mediastinum and highlight the key elements of management of mediastinal paragangliomas. Diagnoses: A left posterior mediastinal mass was found by computed tomography (CT) scan and Chest-enhanced CT. Preoperative ultrasound-guided biopsy suggested the possibility of a paraganglioma. A diagnosis of paraganglioma was established by immunohistochemistry. Interventions: The patient underwent single-stage resection of the lesion via left thoracotomy after preoperative oral α-adrenoceptor (phenoxybenzamine) therapy and intravenous fluid resuscitation for two weeks. Outcomes: The postoperative period was uneventful. The patient exhibited no abnormal blood pressure or recurrence during the 12-month follow-up period. Lessons subsections as per style: Pathological examination alone cannot determine whether it was a benign or malignant paraganglioma, which can be determined by pathological examination combined with distant metastasis. Long-term follow-up is required to assess the treatment effect.

In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected.We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients.We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness.A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).

Objectives: Urine neutrophil gelatinase-associated lipocalin (NGAL) was found to increase in diabetic kidney disease (DKD). However, the clinical value of urine NGAL as diagnostic indicators in DKD remains to be clarified. Methods: Relevant studies were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. Stratified analyses and regression analyses were performed. Results: Fourteen studies with 1561 individuals were included in our analysis, including 1204 cross-sectional participants and 357 cohort participants. For the cross-sectional studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.82 (95% confidence interval (CI): 0.75–0.87) and 0.81 (95% CI: 0.68–0.90), respectively. The pooled diagnostic odds ratio was 19 (95% CI: 11–33), and the overall area under the curve was 0.88 (95% CI: 0.84–0.90). For the cohort studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.96 (95% CI: 0.91–0.98) and 0.89 (95% CI: 0.84–0.92), respectively. The overall area under the curve was 0.98, indicating good discriminative ability of NGAL as biomarkers for DKD. Conclusions: Urine NGAL, as the early diagnostic marker of DKD, might have the high diagnostic value, especially in cohort studies.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients’ tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-β receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.

Background and Purpose— Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. Methods— One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute–subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. Results— Multiple linear regression analyses were completed. Although larger infarcts ( β =0.37, P β =0.39, P β =0.17, P =0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. Conclusions— In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Non‑alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease, affecting up to 30% of the general population worldwide. Non‑alcoholic steatohepatitis (NASH) is a severe form of NAFLD without any effective therapies available. The present study showed that activation of α7‑nicotinic acetylcholine receptor (α7 nAChR) may be a novel potential strategy for NASH therapy. Treatment with the α7 nAChR agonist nicotine for three weeks obviously attenuated hepatic steatosis in a high-fat diet‑induced mouse model of NASH. Investigation of the underlying mechanism showed that nicotine reduced the secretion of the pro‑inflammatory cytokines tumor necrosis factor α and interleukin 6 in vitro and in vivo. Inflammation is an integral part of NASH and is the most prevalent form of hepatic pathology found in the general population; therefore, the effect of α7 nAChR activation against NASH may be ascribed to its anti‑inflammatory effects. In addition, the present study showed that nicotine‑stimulated α7 nAChR activation led to a significant downregulation of nuclear factor kappa B (NK‑κB) and extracellular signal-regulated kinase (ERK). It therefore appeared that activation of α7 nAChR suppressed the production of pro‑inflammatory cytokines through NK‑κB and ERK pathways. In conclusion, the present study indicated that targeting α7 nAChR may represent a novel treatment strategy for NASH.

Background/Aims: Serum/Glucocorticoid Regulated Kinase 1 (SGK1) plays a significant role in regulating renal Na+ reabsorption, K+ secretion, and blood pressure (BP). This study aimed to assess the association of common genetic variants in the SGK1 gene with BP responses to controlled dietary sodium or potassium interventions. Methods: A total of 334 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially maintained a seven-day low-sodium diet (3g/day of NaCl or 51.3mmol/day of sodium), a seven-day high-sodium diet (18g/day of NaCl or 307.8 mmol/day of sodium) and a seven-day high-sodium plus potassium supplementation intervention (4.5g/day of KCl or 60mmol/day of potassium). Six single-nucleotide polymorphisms (SNPs) in the SGK1 gene were selected. Results: After adjustment for multiple testing, SNP rs9376026 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-sodium intervention (P = 0.018 and 0.022, respectively). However, the associations between selected SNPs in the SGK1 gene and BP responses to high-sodium or high-sodium plus potassium-supplementation intervention did not reach statistical significance. In addition, SNP rs9389154 and two other SNPs (rs1763509 and rs9376026) were associated respectively with systolic BP (SBP) and DBP at baseline (P = 0.040, 0.032, and 0.031, respectively). SNP rs3813344 was significantly associated with SBP, DBP, and MAP (P = 0.049, 0.015 and 0.018, respectively). Conclusion: Our study indicates that the genetic polymorphism in the SGK1 gene is significantly associated with BP responses to dietary sodium intervention.

Here, a biodegradable polymer-drug conjugate of doxorubicin (DOX) conjugated with a stearic acid-grafted chitosan oligosaccharide (CSO-SA) was synthesized via disulfide linkers. The obtained polymer-drug conjugate DOX-SS-CSO-SA could self-assemble into nanosized micelles in aqueous medium with a low critical micelle concentration. The size of the micelles was 62.8 nm with a narrow size distribution. In reducing environments, the DOX-SS-CSO-SA could rapidly disassemble result from the cleavage of the disulfide linkers and release the DOX. DOX-SS-CSO-SA had high efficiency for cellular uptake and rapidly released DOX in reductive intracellular environments. In vitro antitumor activity tests showed that the DOX-SS-CSO-SA had higher cytotoxicity against DOX-resistant cells than free DOX, with reversal ability up to 34.8-fold. DOX-SS-CSO-SA altered the drug distribution in vivo, which showed selectively accumulation in tumor and reduced nonspecific accumulation in hearts. In vivo antitumor studies demonstrated that DOX-SS-CSO-SA showed efficient suppression on tumor growth and relieved the DOX-induced cardiac injury. Therefore, DOX-SS-CSO-SA is a potential drug delivery system for safe and effective cancer therapy.

Some studies have proved that both acupuncture and moxibustion are very effective for the treatment of CAG. However, little is known about therapeutic mechanism of electro-acupuncture and moxibustion on CAG as well as the difference between them. On the other hand, metabolomics is a ‘top-down’ approach to understand metabolic changes of organisms caused by disease or interventions in holistic context, which consists with the holistic thinking of electro-acupuncture and moxibustion treatment. In this study, the difference of therapeutic mechanism between electro-acupuncture and moxibustion on CAG rats was investigated by a 1H NMR-based metabolomics analysis of multiple biological samples (serum, stomach, cerebral cortex and medulla) coupled with pathological examination and molecular biological assay. For all sample types, both electro-acupuncture and moxibustion intervention showed beneficial effects by restoring many CAG-induced metabolic changes involved in membrane metabolism, energy metabolism and function of neurotransmitters. Notably, the moxibustion played an important role in CAG treatment mainly by regulating energy metabolism in serum, while main acting site of electro-acupuncture treatment was nervous system in stomach and brain. These findings are helpful to facilitate the therapeutic mechanism elucidating of electro-acupuncture and moxibustion on CAG rats. Metabolomics is promising in mechanisms study for traditional Chinese medicine (TCM).

Objective: This review aimed to provide a current recommendation to multidisciplinary physicians for early detection, diagnosis, and treatment of corticosteroid-induced osteonecrosis of the femoral head (ONFH) based on a comprehensive analysis of the clinical literature. Data Sources: For the purpose of collecting potentially eligible articles, we searched for articles in the PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using the following key words: “corticosteroid”, “osteonecrosis of the femoral head”, “risk factors”, “diagnosis”, “prognosis”, and “treatment”. Study Selection: Articles on relationships between corticosteroid and ONFH were selected for this review. Articles on the diagnosis, prognosis, and intervention of earlier-stage ONFH were also reviewed. Results: The incidence of corticosteroid-induced ONFH was associated with high doses of corticosteroids, and underlying diseases in certain predisposed individuals mainly occurred in the first 3 months of corticosteroid prescription. The enhanced awareness and minimized exposure to the established risk factors and earlier definitive diagnosis are essential for the success of joint preservation. When following up patients with ONFH, treatment should be started if necessary. Surgical treatment yielded better results than conservative therapy in earlier-stage ONFH. The ideal purpose of earlier intervention and treatment is permanent preservation of the femoral head without physical restrictions in daily living. Conclusions: Clinicians should enhance their precaution awareness of corticosteroid-induced ONFH. For high-risk patients, regular follow-up is very important in the 1st year after high-dose prescription of corticosteroids. Patients with suspected ONFH should be referred to orthopedists for diagnosis and treatment in its earlier stage to preserve the joint.

MicroRNA-454 (miR-454) is emerging as critical regulator in tumorigenesis; it may function as an oncogene or a tumor suppressor. However, the role of miR-454 in prostate cancer remains unknown. In this study, we aimed to investigate the function and molecular mechanisms of miR-454 in prostate cancer. We found that miR-454 was highly expressed in prostate cancer tissues and cell lines (*p

Atorvastatin is a member of the statin class of drugs, which competitively inhibit the activity of 5‑hydroxy‑3‑methylglutaryl‑coenzyme A reductase. The aim of the present study was to assess whether atorvastatin may protect BV‑2 microglia and hippocampal neurons against oxygen‑glucose deprivation (OGD)‑induced neuronal inflammatory injury and to determine the underlying mechanisms by which its effects are produced. Cell viability and apoptotic ability were assessed using an MTT assay and annexin V‑fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometry, respectively. The expression of inflammation and apoptosis‑associated mRNAs and proteins were assessed using reverse transcription‑quantitative polymerase chain reaction and western blotting, and the expression of inflammatory factors was determined using ELISA. The results of the current study revealed that atorvastatin treatment suppressed the viability of OGD BV‑2 microglia and hippocampal neurons. Furthermore, atorvastatin treatment reduced the expression of proinflammatory factors in OGD BV‑2 microglia. Additionally, it was demonstrated to downregulate the toll‑like receptor 4 (TLR4)/tumor necrosis factor receptor‑associated factor 6 (TRAF6)/nuclear factor‑κB (NF‑κB) pathway in OGD BV‑2 microglia. Atorvastatin also inhibited the apoptosis of OGD hippocampal neurons by regulating the expression of apoptosis‑associated proteins. It was concluded that atorvastatin treatment may protect BV‑2 microglia and hippocampal neurons from OGD‑induced neuronal inflammatory injury by suppressing the TLR4/TRAF6/NF‑κB pathway. This may provide a potential strategy for the treatment of neuronal injury.

Background Hepatic cell carcinoma (HCC) is more common in clinical practice, and has high malignant degree. Objective This study aims to analyze the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating hepatic cell carcinoma (HCC) and its effect on serum markers. Methods A total of 106 cases of patients with hepatic cell carcinoma treated in our hospital were randomly divided into two groups: observation group and control group. Patients in the observation group (53 cases) received transcatheter arterial chemoembolization combined with radiofrequency ablation therapy, while subjects in the control group (53 cases) received transcatheter arterial chemoembolization therapy. Differences in the overall effect, indicators of inflammation and oxidative stress, tumor activity-related indicators and tumor recurrence-related indicators between these two groups were compared. Results At one and two weeks after treatment, the number of cases of CR and PR in the observation group was higher than that in the control group, the number of cases of SD was not different from that in the control group, and the number of cases of PD was lower than that in the control group. At two weeks after treatment, differences in serum MDA, SOD, GSH, CRP, TNF-α and ESR between the two groups were significant. However, serum EC, VEGF, MMP, AFP, CA199 and GGT content was significantly lower in the observation group than that in the control group. Conclutions Transcatheter arterial chemoembolization combined with radiofrequency ablation therapy can effectively control the growth of liver cancer lesions, reduce the levels of tumor-related serum markers, and inhibit the activity of tumor cells.

Many studies have revealed apolipoproteins are risk factors for ischemic stroke, but the influence of apolipoproteins on onset age of first-ever atherosclerotic stroke has not been well investigated.We recruited 357 qualified participants from consecutive patients with acute ischemic stroke who came to the stroke registry center in Sichuan Provincial People's Hospital, Chengdu, China. Patients were stratified into tertiles according to the distributions of apoB levels for large artery atherosclerosis (LAA) and small artery atherosclerosis (SAA) groups. The onset age of stroke was analyzed tripartitely in terms of early-onset group, the middling-onset group and the late-onset group. Multinomial logistical regression was used to analyze the associations between the two.The risk of early-onset stroke increased monotonically with higher apoB levels (the second tertile, adjusted OR = 2.61, 95% CI 1.18-5.79 (p = 0.018); the third tertile, adjusted OR = 19.52, 95% CI 5.93-64.31 (p0.001)), and patients with the highest tertile of apoB levels had a 9.20 times (95% CI, 2.97-28.53, p0.001) increased risk of middling-onset stroke in reference to late onset of stroke.The present study suggests the higher the apolipoprotein B levels are, the earlier an atherosclerotic stroke might occur in a Chinese population.

The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.

Electrocardiographic characteristics of Wellens syndrome (WS) consist of deeply inverted T waves or biphasic T waves in anterior precordial leads. Studies have shown that patients with WS have critical stenosis or complete obstruction of the proximal left anterior descending coronary artery (LAD) and high risk for the development of extensive anterior myocardial infarction. Here, we reported a case presenting with WS and with a small plaque in the proximal LAD and slow flow in the LAD other than significant stenosis of the proximal LAD detected by coronary angiography. The mechanisms for WS of our case are discussed.

Diabetic encephalopathy (DE) is one of the severe complications in patients with diabetes mellitus. Paeonol, an active compound isolated from the root bark of Paeonia suffruticosa, has significant antidiabetic activity in vivo. However, its underlying beneficial effects on DE were unclear. In the present study, the protective activity of paeonol on DE was evaluated in streptozotocin (STZ)-induced diabetic rats. Paeonol at 50 and 100 mg/kg significantly increased body weight and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation end products (AGEs) levels. Immunohistochemistry assays and Western blot analysis revealed a significant decrease in expressions on receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NF-κB) in hippocampus and cerebral cortical neurons after paeonol treatment. Furthermore, paeonol significantly increased glutathione content and remarkedly decreased induced nitric oxide synthase activity in hippocampus tissue. Our findings indicated that paeonol could improve the pathological damage of DE in STZ-induced diabetic rats. It might be associated with the modulating AGEs/RAGE/NF-κB pathway. This study suggested that paeonol might be a promising candidate for the prevention and treatment of DE.

This study was designed to assess the clinical effect of bone marrow mononuclear cells including mesenchymal stem cell (MSCs) in patients with intracerebral hemorrhage (ICH).One hundred patients were divided into a study (n=60) or a control group (n=40). Bone marrow mononuclear cells from the same patient were injected to the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.9 days after ICH. National Institute Stroke Scale (NIHSSS) and Barthel index was used to assess neurologic impairment and daily activities, respectively, before and 6 months after intervention.Six months after implantation, the NIHSS score in the study group was lower than in the control group (10.09 ± 8.86 vs 14.35 ± 10.14, P0.01), whereas the Barthel scores were higher (57.39 ± 23.51 vs 46.90 ± 20.29, P0.01). Neurological and functional improvement was observed in 52 (86.7%) of the study group patients, and in 17 (42.5%) of the control group patients (P=0.001). No allergic or other adverse effects were observed in the study group.Autologous bone marrow mononuclear cell implantation reduced neurological impairment and improved activities of daily living in a selected group of ICH patients. Further studies are required to ascertain the long-term safety and efficacy of this treatment.

BACKGROUND Excess dietary salt is strongly correlated with cardiovascular disease, morbidity, and mortality. Conversely, potassium likely elicits favorable effects on cardiovascular disorders. In epidemiological studies, increased plasma osteoprotegerin (OPG) concentrations are associated with atherosclerosis and vascular deaths. Our study was designed to examine the effects of salt intake and potassium supplementation on plasma OPG levels in normotensive subjects.Methods and Results:The 18 normotensive subjects were selected from a rural community in China. They were sequentially maintained on low-salt diet for 7 days (3 g/day, NaCl), high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for 7 days (18 g/day of NaCl+4.5 g/day of KCl). High-salt intake enhanced plasma OPG levels (252.7±13.9 vs. 293.4±16.1 pg/mL). This phenomenon was abolished through potassium supplementation (293.4±16.1 vs. 235.1±11.3 pg/mL). Further analyses revealed that the OPG concentration positively correlated with 24-h urinary sodium excretion (r=0.497, P

AIM To investigate the prevalence of depression and anxiety in patients with chronic digestive system diseases. METHODS A total of 1736 patients with chronic digestive system diseases were included in this cross-sectional study, including 871 outpatients and 865 in-patients. A self-designed General Information for Patients of the Department of Gastroenterology of General Hospitals questionnaire was used to collect each patient’s general information, which included demographic data (including age, sex, marital status, and education) and disease characteristics (including major diseases, disease duration, principal symptoms, chronic pain, sleep disorder, and limited daily activities). RESULTS The overall detection rate was 31.11% (540/1736) for depression symptoms alone, 27.02% (469/1736) for anxiety symptoms alone, 20.68% (359/1736) for both depression and anxiety symptoms, and 37.44% (650/1736) for either depression or anxiety symptoms. Subjects aged 70 years or above had the highest detection rate of depression (44.06%) and anxiety symptoms (33.33%). χ2 trend test showed: the higher the body mass index (BMI), the lower the detection rate of depression and anxiety symptoms (χ2trend = 13.697, P < 0.001; χ2trend = 9.082, P = 0.003); the more severe the limited daily activities, the higher the detection rate of depression and anxiety symptoms (χ2trend = 130.455, P < 0.001, χ2trend = 108.528, P < 0.001); and the poorer the sleep quality, the higher the detection rate of depression and anxiety symptoms (χ2trend = 85.759, P < 0.001; χ2trend = 51.969, P < 0.001). Patients with digestive system tumors had the highest detection rate of depression (57.55%) and anxiety (55.19%), followed by patients with liver cirrhosis (41.35% and 48.08%). Depression and anxiety symptoms were also high in subjects with comorbid hypertension and coronary heart disease. CONCLUSION Depression and anxiety occur in patients with tumors, liver cirrhosis, functional dyspepsia, and chronic viral hepatitis. Elderly, divorced/widowed, poor sleep quality, and lower BMI are associated with higher risk of depression and anxiety.

BACKGROUND Blood pressure (BP) variability has been shown to be an independent risk factor of stroke and target organ damage because of hypertension, but so far, there have been very few studies investigating the impact of BP variability on cerebrovascular atherosclerosis. METHODS A total of 409 participants were enrolled and classified according to patterns of cerebrovascular atherosclerosis (i.e. large or small artery atherosclerosis; extracranial; or intracranial artery atherosclerosis). Coefficient of variation (CV) was used as a marker of BP variability. Multivariate binary logistical regression was used to analyze the associations between BP variability and the risk of different patterns of cerebrovascular atherosclerosis. RESULTS The risk of large artery atherosclerosis and extracranial arterial stenosis, respectively, had a dose-responsive positive relationship with the tertiles of awake systolic blood pressure (SBP) CVs [large artery atherosclerosis, the second tertile, adjusted odds ratio (OR)=2.839, 95% confidence interval (CI) 1.593-5.059, P

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT). A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases. Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P 140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model. Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

Background: Percutaneous endoscopic interlaminar discectomy (PEID), which poses advantages for certain types of herniated disc, is gaining wider acceptance in clinical practice. We retrospectively analyzed the efficacy of the PEID technique in treatment of calcified lumbar disc herniation. Study Design: A retrospective case-control study. Setting: University hospital in China. Objective: To evaluate the efficacy of the PEID technique in treatment of calcified lumbar disc herniation, and a comparison between calcified and noncalcified disc herniation was drawn to analyze the causes of herniated disc calcification. Methods: Data from patients who underwent full-endoscopic lumbar discectomy in our department between March 2011 and May 2013 were collected. Thirty cases with calcified lumbar disc herniation were included in the study group, and 30 age-, gender-, and body mass index (BMI)-matched cases with noncalcified lumbar disc herniation served as controls. Perioperative data, preoperative and postoperative Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) values, MacNab scores, and postoperative low-extremity dysesthesia among patients in the 2 groups were collected. Results: The values of computed tomography (CT) in the calcified group were significantly higher than those in the noncalcified group (P < 0.01). The preoperative disease courses in the 2 groups were similar. However, there was a statistically significant difference in the duration of traditional Chinese medicines (TCM) administration (P < 0.01). VAS and ODI scores improved significantly after surgery, but there were no significant differences between the 2 groups (P > 0.05). Three months after surgery, the rate of low-extremity dysesthesia in the calcified group was significantly higher than that in the control group (P = 0.03) but became similar at 6 months. By applying MacNab criteria the proportions of good and excellent were greater than 90% in both groups, and there was no difference between groups (P > 0.05). Limitations: The sample size was small in this retrospective study. Conclusion: The PEID technique is an effective method in the treatment of calcified lumber disc herniation, although the rate of postoperative dysesthesia is higher in this group during the early postoperative period. Long-term TCM administration may be related to the calcification of herniated lumbar discs. Key words: Lumbar disc herniation, percutaneous endoscopic lumbar discectomy, interlaminar approach, calcification

At present, the fundamental frequencies of signals of most commercially available acoustic alarms to deter small cetaceans are below 20 kHz, but it is not well ascertained whether higher frequencies have a deterrent effect on bottlenose dolphins (Tursiops truncatus). Two captive bottlenose dolphins housed in a floating pen were subjected to a continuous pure tone at 50 kHz with a source level of 160 ± 2 dB (re 1 μPa, rms). The behavioral responses of dolphins were judged by comparing surfacing distance relative to the sound source, number of surfacings, and number of echolocation clicks produced, during forty 15 min baseline periods with forty 15 min test periods (four sessions per day, 40 sessions in total). On all 10 study days, surfacing distance and the number of surfacings increased while click production decreased during broadcasts of test sound. The avoidance threshold sound pressure level for a continuous 50 kHz tone for the bottlenose dolphins, in the context of this study, was estimated to be 144 ± 2 dB (re 1 μPa, rms). The results indicated that a continuous 50 kHz tonal signal can deter bottlenose dolphins from an area.