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Background Closed reduction and pinning entry fixation have been proposed as treatment strategies for displaced supracondylar humeral fractures (SCHFs) in children. However, controversy exists regarding the selection of the appropriate procedure. Hence, this meta-analysis was conducted to compare the effect of lateral and crossed pin fixation for pediatric SCHFs, providing a reference for clinical treatment. Methods Online databases were systematically searched for randomized controlled trials (RCTs) comparing lateral pinning entry and crossed pinning entry for children with SCHFs. The primary endpoints were iatrogenic ulnar nerve injuries, complications, and radiographic and functional outcomes. Results Our results showed that iatrogenic ulnar nerve injuries occurred more commonly in the crossed pinning entry group than in the lateral pinning entry group (RR = 4.41, 95% CI 1.97–9.86, P < 0.05). However, its risk between the crossed pinning with mini-open incisions group and the lateral pinning entry group was not significantly different (RR = 1.58, 95% CI 0.008–29.57, P = 0.76). The loss of reduction risk was higher in the lateral pinning entry group than in the crossed pinning entry group (RR = 0.66; 95% CI 0.49–0.89, P < 0.05). There were no significant differences in the carry angle, Baumann angle, Flynn scores, infections, and other complications between these two groups. Conclusions The crossed pinning entry with mini-open incision technique reduced the loss of reduction risk, and the risk of iatrogenic ulnar nerve injury was lower than in the lateral pinning entry group. The crossed pinning entry with mini-open incision technique is an effective therapeutic strategy for managing displaced supracondylar humeral fractures in children.

Interleukin-12 (IL-12) and IL-23 are thought to have central roles in inflammation and are critical to pathologies associated with inflammation-induced bone disorders. The deletion of IL-12p40 (a common subunit of IL-12 and IL-23) can improve bone regeneration. However, the relative roles of IL-12 and IL-23 in bone disorders are largely unknown. Methods: Ectopic bone formation and skull defect models were established to evaluate the relative roles of IL-12 and IL-23 in inflammatory bone disorders. Differences in bone mass among WT, IL-12p35-/-, and IL-12p40-/- mice (young and elderly) were detected by micro-CT. Osteogenic and osteoclastic activities were explored using ELISA, qRT-PCR, and histological analysis. Moreover, the mechanisms by which IL-12 and IL-23 regulated the differentiation of BMMSCs and RAW264.7 cells were explored using Alizarin Red and tartrate-resistant acid phosphatase staining in vitro. Apilimod was used to inhibit IL-12 and IL-23 production in vivo. Results: Mice deficient in IL-12p40 promoted bone formation and protected against aging-related bone loss. By contrast, bone loss was aggravated in IL-12-/- mice, suggesting that IL-23 may play a dominant role in inflammation-related bone disorders. Mechanistically, IL-12 and IL-23 coupled osteogenesis and osteoclastic activities to regulate bone homeostasis and repair. IL-23 deficiency increased bone formation and inhibited bone resorption. Finally, apilimod treatment significantly improved bone regeneration and calvarial defect repair. Conclusion: These data collectively uncover a previously unrecognized role of IL-23 in skeletal tissue engineering. Thus, IL-23 can act as a biomarker to predict diseases and treatment efficacy, and apilimod can be used as an effective therapeutic drug to combat inflammatory bone disorders.

Primary health care has been emphasized as a pillar of China’s current round of health reforms throughout the previous decade. The purpose of this study is to analyze the accessibility of primary health care services in Beijing and to identify locations with a relative scarcity of health personnel. Seven ecological conservation districts, which are relatively underdeveloped, were selected in the study. The Gini coefficient and Lorenz curve, as well as the shortest trip time and modified two-step floating catchment area (M2SFCA) approach, are used to quantify inequalities in primary health care resources and spatial accessibility. The Gini coefficient of primary medical services was calculated as high as 0.705, showing a significant disparity in primary care services. A total of 81.22% of communities reached the nearest primary care institution within 15 min. The average accessibility of primary healthcare services, as measured by the number of health professionals per 1000 population, was 2.34 in the 1715 communities of seven ecological conservation districts. Three hundred and ninety-one communities (22.80%) were identified with relatively low accessibility. More primary health professionals should be allocated to Miyun, Mentougou, and Changping Districts. Overall, the primary healthcare resources were distributed unevenly in most districts. According to our study, expanding primary healthcare institutions, increasing the number of competent health professionals, and enhancing road networks will all be effective ways to increase spatial accessibility and reduce primary healthcare service disparity in Beijing.

Background: Chronic alcohol is one of the leading risk factors for male osteoporosis . Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. It is unknown whether alcohol inhibits type-H-vessel-dependent bone formation. Aims: This study aimed to determine whether alcohol hampers proliferation and promotes aging of endothelial cells of type-H vessels, and whether alcohol inhibits the differentiation of bone marrow-mesenchymal stem cells (BM-MSCs) into osteoblasts through reducing the number and secretion of endothelial cells in type-H vessels. Materials and Methods: Two-month-old mice fed with alcohol liquid diet (28% of calories) or normal liquid diet for two months. The tibias were isolated and detected with X-ray and micro-CT. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining respectively in vivo . Human Umbilical Vein Endothelial Cells (HUVECs) were treated with different-concentrated alcohol for 12 hours. The conditioned medium of the above HUVECs cells was collected to culture human BM-MSCs, which were induced to differentiate into osteoblasts in vitro . Results: The alcoholic diet retarded the bone growth and lead to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1 and BMP2 compared to vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Conclusions: Alcoholic diet impaired CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells via Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. It provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H-vessel to prevent alcoholic osteopenia.

This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1–deficient (Bmi-1–/–), Bmi-1 and p16INK4a double-knockout (Bmi-1–/–p16INK4a–/–), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)–dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1–/– and Bmi-1–/–p16INK4a–/– mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1–/– mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α–dependent barrier permeability and aging. Accumulated p16INK4a combined with occludin at the 1st–160th residue in cytoplasm of intestinal epithelium cells from Bmi-1–/– mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16INK4a deletion could maintain barrier function and microbiota balance in Bmi-1–/– mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16INK4a accumulation. The clearance of p16INK4a-positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1–160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16INK4a with occludin for protecting TJ.

SCOPE Liver plays a central role in maintaining lipid homeostasis which is dysregulated in non-alcoholic fatty liver disease (NAFLD) caused by overload of dietary fat, increase in lipid synthesis, and alteration of fatty acid oxidation in the liver. In this study, we aimed to investigate whether intermittent calorie restriction using a fasting-mimicking diet (FMD) is able to slow down the progression of NAFLD in mice. METHODS AND RESULTS This study analyzed the intervention activity of a FMD low in carbohydrate/protein but high in dietary fibers with a NAFLD mouse model induced by high-fat high-sucrose diet (HFHSD). Intermittent application of the FMD reduces HFHSD-induced obesity and glucose intolerance. The FMD decreases the size of adipocytes and elevates expression of lipolysis genes and HSL protein in white adipose tissue. HFHSD-induced lipid accumulation in the liver is reduced by the FMD, accompanied by a reduction of macrophage marker in the liver. RNA sequencing reveals that the expression of a number of genes involved in fatty acid oxidation is elevated by the FMD. CONCLUSION The findings indicate that intermittent application of the FMD can improve NAFLD, at least in part, through increased lipolysis in white adipose tissue and elevated fatty acid oxidation in the liver.

MicroRNAs play important roles in osteoporosis and show great potential for diagnosis and therapy of osteoporosis. Previous studies have demonstrated that miR-146a affects osteoblast (OB) and osteoclast (OC) formation. However, these findings have yet to be identified in vivo, and it is unclear whether miR-146a is related to postmenopausal osteoporosis. Here, we demonstrated that miR-146a knockout protects bone loss in mouse model of estrogen-deficient osteoporosis, and miR-146a inhibits OB and OC activities in vitro and in vivo. MiR-146a-/- mice displayed the same bone mass as the wild type (WT) but exhibited a stronger bone turnover than the WT did under normal conditions. Nevertheless, miR-146a-/- mice showed an increase in bone mass after undergoing ovariectomy (OVX) compared with those subjected to sham operation. OC activities were impaired in the miR-146a-/- mice exposed to estrogen deficiency, which was diametrically opposite to the enhanced bone resorption ability of WT. Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) from a bone microenvironment affect this extraordinary phenomenon. Therefore, our results implicate that miR-146a plays a key role in estrogen deficiency-induced osteoporosis, and the inhibition of this molecule provides skeleton protection. © 2019 American Society for Bone and Mineral Research.

Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional efficacy of intermittent CR to continuous CR in metabolic disorders such as diabetes. In this study, we analyzed two regimes of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2-5 or 5-9 regimes followed by free eating for 5 or 9 days respectively). In the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models. In conclusion, our study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving insulin sensitivity. Funding Statement: This study was supported by research grants from the National Natural Science Foundation of China (31630036 to Y.C.), the Ministry of Science and Technology of China (2016YFA0500103 to Y.C.), and the Chinese Academy of Sciences (XDA12010102, QYZDJ-SSW-SMC008, ZDRW-ZS-2016-8, and Y817X11141 to Y.C Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal experiments were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) with an approval number 2010-AN-8.

Low-density lipoprotein cholesterol (LDL-C) is the hallmark of atherosclerotic cardiovascular diseases. The hepatic LDL receptor (LDLR) plays an important role in clearance of circulating LDL-C. PCSK9 facilitates degradation of LDLR in the lysosome and antagonizing PCSK9 has been successfully used in the clinic to reduce blood LDL-C level. Here we identify a new player that modulates LDLR interaction with PCSK9, thus controlling LDLR degradation and cholesterol homeostasis.The blood LDL-C and cholesterol levels were analyzed in mice with hepatic deletion of Paqr3 gene. The half-life of LDLR was analyzed in HepG2 cells. The interaction of PAQR3 with LDLR and PCSK9 was analyzed by co-immunoprecipitation and immunofluorescent staining.The blood LDL-C and total cholesterol levels in the mice with hepatic deletion of Paqr3 gene were significantly lower than the control mice after feeding with high-fat diet (p 0.001 and p 0.05 respectively). The steady-state level of LDLR protein is elevated by Paqr3 knockdown/deletion and reduced by PAQR3 overexpression. The half-life of LDLR protein is increased by Paqr3 knockdown and accelerated by PAQR3 overexpression. PAQR3 interacts with the β-sheet domain of LDLR and the P-domain of PCSK9 respectively. In addition, PAQR3 can be localized in early endosomes and colocalized with LDLR, PCSK9 and LDL. Mechanistically, PAQR3 enhances the interaction between LDLR and PCSK9.Our study reveals that PAQR3 plays a pivotal role in controlling hepatic LDLR degradation and blood LDL-C level via modulating LDLR-PCSK9 interaction.

PIP5k1β is crucial to the generation of phosphotidylinosotol (4, 5)P2. PIP5k1β participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to examine the function of PIP5k1β in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation. Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation. PIP5k1β−/− osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1β deficiency also promoted activation of mitogen-activated kinase and Akt signaling, enhanced TRAF6 and c-Fos expression, facilitated the expression and nuclear translocation of NFATC1, and upregulated Grb2 expression, thereby accelerating osteoclast differentiation and function. Finally, PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling. Therefore, PIP5k1β modulates bone homeostasis and remodeling.

Background Introduction Multiple sclerosis(MS) is a common complication of uncontrolled or excessive neuroinflammation and autoimmunity disease. Advances in high-throughput technologies and available bioinformatics tools make it possible to evaluate different expressions in the whole genome instead of focusing on a limited number of genes. MethodsMaterials and methods Two public available databases GSE81279 and GSE21942 of multiple sclerosis samples were downloaded analyzed by CIBERSORT. Gene Ontology (GO) and KEGG pathway analysis based on GSEA was performed by cluster profile software to reveal the regulatory relations among genes and provided a systematic understanding of the functional differentially expressed genes at the transcriptional level.GSE81279 was used to validate the association between core genes and clinical information. ResultsFor immune cells, T-cell gamma delta and monocyte showed a trend toward reduction. The connection between the most prominent GO terms showed HBB, GATA2, NAA35, TCL1A, SECISBP2L, CLC, AGPAT5, CCR3, LTF, MALAT1, MS4A3 were significantly differentially expressed in MS. Gene set enrichment result was presented CDKN1A, DDB2, MME HMGN1, XPC, RELA for subsequent analysis.GSE81279 showed five types of immune cells revealed important links with MS. GSEA and layered KEGG analyses revealed that enrichment of immune response-related in primary immunodeficiency, it also consistent with previous studies. We got 10 genes, including HLA-DR, IL7R, HBB, TNFRSF1A, CYP27B1, NR1H3, IL2RA, TNFR1, BAFF, and CYP2R1 had close connections to clinical features. ConclusionsOur study identifies immune cell infiltration with microarray data of the plasma in MS by using CIBERSORT analysis, we also provide novel information for further study of genes of multiple sclerosis.

Intermittent slug flow pattern commonly occurs in industrial processes, including petroleum, nuclear and chemical fields. Therefore, it is important to measure its characteristic parameters. The aim of this paper is to measure the liquid film thickness under elongated bubbles based on laser-induced fluorescence method. A new image processing procedure is developed to extract the axial liquid film thickness. To improve the robustness of the method, image enhancement and threshold segmentation algorithms are developed respectively. Based on the statistical analysis method, the influence of superficial gas-liquid velocity on the liquid film thickness is discussed. Furthermore, the frequency domain features of the liquid film thickness are also used to characterize the flow pattern transition from plug flow to slug flow. Finally, the experimental results show that the measured liquid film thickness is higher than the model predictions, and the relative error is within 8.6%.

Annular flow is a common flow pattern of gas-liquid flow, which often occurs in many industrial applications. Based on the planar laser-induced fluorescence (PLIF) method and the digital image processing, the thickness of the liquid film in the vertical upward annular flow is obtained. The effect of the gas and liquid superficial velocity on the liquid film thickness and wave structure in annular flow is studied by the wavelet multi-resolution analysis. The variations of waves at different frequencies with the gas and liquid superficial velocity is discussed.

Fat storage and mobilization in adipose tissue play a central role in energy metabolism and are directly linked to the development of obesity. Upon starvation, fat is mobilized from adipose tissue by lipolysis, a process by which triglycerides are hydrolyzed to free fatty acids to be used as an energy source in skeletal muscles and other tissues. However, how lipolysis is activated by starvation is not fully known. In this study, we demonstrate that PAQR11, a member of the progesterone and AdipoQ receptor family, regulates starvation-mediated lipolysis. Paqr11-deleted mice are resistant to high-fat diet-induced obesity. Paqr11 deletion promotes lipolysis in white adipose tissue, characterized by increased phosphorylations of hormone-sensitive lipase (HSL) and perilipin 1 (PLIN1) and elevated serum levels of glycerol and free fatty acids. PKA activity and cAMP levels in white adipose tissue are also increased by Paqr11 deletion, accompanied by accelerated protein degradation of phosphodiesterase 4D (PDE4D). Mechanistically, PAQR11 decreases the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex, thus modulating the polyubiquitination/degradation of PDE4D. Fasting decreases the expression of the Paqr11 gene, and starvation-induced lipolysis in white adipose tissue is enhanced by Paqr11 deletion, while insulin-mediated suppression of lipolysis is not affected. Collectively, these results reveal that PAQR11 regulates lipolysis of adipose tissue and affects high-fat diet-induced obesity., Highlights • Paqr11 deletion promotes lipolysis in epididymal white adipose tissue. • PAQR11 modulates cAMP level by altering protein degradation of PDE4D. • PAQR11 affects the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex. • PAQR11 regulates starvation-induced lipolysis in adipose tissue.

Pure red cell aplasia (PRCA) is a rare syndrome characterized by severe anemia and absence of erythroid precursors. PRCA associated to monoclonal gammopathy of undetermined significance (MGUS) is a scarce condition with less than five cases reported so far. There is no agreement on the treatment of MGUS associated PRCA and treatment- free survival (TFS) is an unmet clinical need. In this report, for the first time, we demonstrated two patients with MGUS associated PRCA obtained rapid remission and maintained TFS after accepting intensive short-term bortezomib plus dexamethasone. The first case was refractory to cyclosporine and prednisone, but achieved complete remission after ten doses of bortezomib. Moreover, he has kept TFS for 12 months. The other case initiated bortezomib plus dexamethasone as soon as making a definite diagnosis. She obtained complete remission after twelve doses of bortezomib and she has maintained a normal level of haemoglobin for 8 months.

Refractory IDA and chronic occult bleeding from GI tract could happen due to BRBNS. Clinicians should keep in mind to detect the underlying diseases from GI tract by endoscopy. Precision diagnosis and appropriate intervention could booster to upgrade the quality of life for patients.

Background Mesenchymal stromal cells (MSCs) are an emerging prophylaxis option for graft-versus-host disease (GVHD) in haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) recipients with severe aplastic anemia (SAA), but studies have reported inconsistent results. This systematic review and meta-analysis evaluates the efficacy of MSCs as prophylaxis for GVHD in SAA patients with haplo-HSCT. Methods Studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, and http://clinicaltrials.gov from establishment to February 2020. Twenty-nine single-arm studies (n = 1456) were included, in which eight (n = 241) studies combined with MSCs and eleven (n = 1215) reports without MSCs in haplo-HSCT for SAA patients. The primary outcomes were the incidences of GVHD. Other outcomes included 2-year overall survival (OS) and the incidence of cytomegalovirus (CMV) infection. Odds ratios (ORs) were calculated to compare the results pooled through random or fixed effects models. Results Between MSCs and no MSCs groups, no significant differences were found in the pooled incidences of acute GVHD (56.0%, 95% CI 48.6–63.5% vs. 47.2%, 95% CI 29.0–65.4%; OR 1.43, 95% CI 0.91–2.25; p = 0.123), grade II–IV acute GVHD (29.8%, 95% CI 24.1–35.5% vs. 30.6%, 95% CI 26.6–34.6%; OR 0.97, 95% CI 0.70–1.32; p = 0.889), and chronic GVHD (25.4%, 95% CI 19.8–31.0% vs. 30.0%, 95% CI 23.3–36.6%; OR 0.79, 95% CI 0.56–1.11; p = 0.187). Furtherly, there was no obvious difference in 2-year OS (OR 0.98, 95% CI 0.60–1.61; p = 1.000) and incidence of CMV infection (OR 0.61, 95% CI 0.40–1.92; p = 0.018). Conclusions Our meta-analysis indicates that the prophylactic use of MSC co-transplantation is not an effective option for SAA patients undergoing haplo-HSCT. Hence, the general co-transplantation of MSCs for SAA haplo-HSCT recipients may lack evidence-based practice.

Morphological changes, e.g. thickness of retinal or choroidal layers in Optical coherence tomography (OCT), is of great importance in clinic applications as they reveal some specific eye diseases and other systemic conditions. However, there are many challenges in the accurate segmentation of retinal and choroidal layers, such as low contrast between different tissue layers and variations between images acquired from multiple devices. There is a strong demand on accurate and robust segmentation models with high generalization ability to deal with images from different devices. This paper proposes a new unsupervised guided adversarial adaptation (GAA) network to segment both retinal layers and the choroid in OCT images. To our best knowledge, this is the first work to extract retinal and choroidal layers in a unified manner. It first introduces a dual encoder structure to ensure that the encoding path of the source domain image is independent of that of the target domain image. By integrating the dual encoder into an adversarial framework, the holistic GAA network significantly alleviates the performance degradation of the source domain image segmentation caused by parameter entanglement with the encoder of the target domain and also improves the segmentation performance of the target domain images. Experimental results show that the proposed network outperforms other state-of-the-art methods in retinal and choroidal layer segmentation.

Background. Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder that severely affects patients’ life. Moxibustion is believed to be an effective way to treat IBS-D. However, the therapeutic effects and the underlying mechanisms in symptom management of IBS-D by different moxibustion therapies remain unclear. Methods. IBS-D model rats were divided into groups and treated with ginger-partitioned moxibustion (GPM), mild moxibustion (MM), and laser moxibustion (LM) at a temperature of 43°C, respectively. The temperature curves of acupoints were recorded during interventions. The therapeutic effects were evaluated on the basis of general condition, stool, and hematoxylin-eosin staining of the colon tissue. Moreover, the expression of transient receptor potential vanilloid 1 (TRPV1) receptors in both acupoint tissue and colon tissue was analyzed by immunohistochemistry. Results. After moxibustion treatment, the symptoms were improved. The expression of TRPV1 was increased in acupoint tissue and decreased in colon tissue. GPM and MM showed a more significant influence on IBS-D rats compared with LM. The temperature profile of GPM and MM was wave-like, while LM had an almost stable temperature curve. Conclusion. GPM, MM, and LM could improve the symptoms in IBS-D rats. Moxibustion might activate TRPV1 channels in the acupoint tissue and induce acupoint functions, which in turn inhibit the pathological activation state of the colon’s TRPV1, followed by improvements in abdominal pain and diarrheal symptoms. LM with stable temperature might lead to the desensitization of TRPV1 receptors and the tolerance of acupoint. GPM and MM provided dynamic and repetitive thermal stimulations that perhaps induced acupoint sensitization to increase efficacy. Therefore, dynamic and repetitive thermal stimulation is recommended in the application of moxibustion.

Background Interleukin (IL) 28B polymorphisms encoding pro-inflammatory and anti-inflammatory cytokines trigger diverse clinical outcome of hepatitis virus infection. However, there is controversy concerning the association of IL28B polymorphisms with the outcome of hepatitis B virus (HBV) infection, with several studies obtaining inconsistent results. We performed a meta-analysis to evaluate the role of 3 single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 in the progression of HBV infection, overall and by ethnicity. Methods Searched PubMed, Embase and Wiley Online Library electronic databases using ‘interleukin 28B’, ‘IL 28B’, ‘IL 28B polymorphism’, ‘hepatitis B virus’, ‘HBV’, and performed meta- analysis for rs12979860, rs12980275 and rs8099917 in Asian and Caucasian populations under the dominant recessive and allele model. Results Eighteen studies were found in total and used for this meta-analysis, including 5587 cases and 4295 controls. The IL28B polymorphism rs12979860 had no association with HBV persistence (CC vs CT + TT: OR = 0.86, 95% CI = 0.76–1.00; TT vs CT + CC: OR = 1.14, 95% CI = 0.76–1.70; T vs C: OR = 1.03, 95% CI = 0.94–1.13). Similarly, neither rs12980275 nor rs8099917 had associations with HBV persistence (rs12980275 in AA vs AG + AA: OR = 1.15, 95% CI = 0.96–1.38; rs8099917 in TT vs GT + GG: OR = 1.15, 95% CI = 0.96–1.39). There was also no significant association of IL28B polymorphisms with persistent HBV infection in Asians or Chinese. There was no evidence of an association of rs12979860 with the HBV-related hepatocellular carcinoma susceptibility (T vs C: OR = 1.53, 95% CI = 0.96–2.43). Conclusion IL28B polymorphisms had no association with the outcome of HBV infection overall, nor in the Asians and the Chinese. These 3 SNPs might not be relevant to the development of HBV infection.

Scope Low circulating 25-hydroxyvitamin D (25(OH)D) levels associate with obesity, diabetes, and hyperlipidemia, but the underlying mechanisms remain uncertain. As energy-dense diet contributes to these disorders, this study investigates whether diet could impair vitamin D metabolism. Methods and results Compared with control chow-fed mice, high fat diet (HFD)-fed mice show lower serum 25(OH)D3 and 1,25(OH)2 D3 levels, lower hepatic vitamin D 25-hydroxylase Cyp2r1 expression but comparable renal vitamin D metabolic enzymes expression. Time course studies show that after HFD feeding, the serum concentrations of cholesterol, triglycerides, fatty acids, glucose, and insulin elevate sequentially and before the reduction of hepatic Cyp2r1 expression and serum 25(OH)D3 levels. Hepatic Cyp2r1 expression also reduces after consuming high fat and high sucrose diet. After high cholesterol diet feeding, serum total cholesterol rises and hepatic Cyp2r1 expression decreases ahead of the reduction of serum 25(OH)D3 . In vitro studies demonstrate that high concentrations of cholesterol, glucose, and insulin significantly inhibit Cyp2r1expression in primary murine hepatocytes. Further studies show that dietary restriction in HFD-fed mice ameliorates hypercholesterolemia, hyperglycemia, and hypertriglyceridemia, and elevates hepatic Cyp2r1 expression and serum 25(OH)D3 level. Conclusion These findings suggest that diet-induced elevation of circulating cholesterol, glucose, and insulin reduces serum 25(OH)D3 level through suppressing hepatic Cyp2r1 expression.

Introduction Peanuts are widely consumed as a meal ingredient and a snack, and are commonly considered as a healthy food based on their nutrient profile. Peanut consumption has been associated with a lower risk of metabolic syndrome (MetS) in epidemiological studies. This study aims to investigate whether consuming peanuts affects the gut microbiota in adults with risk of MetS and whether the intervention effect of peanuts is associated with gut microbiota composition. Methods and results This study analyzes the gut microbiota of subjects from a 12-week randomized clinical trial comparing consumption of either peanuts or isocaloric carbohydrate bars. It is observed that there is high inter-individual variability on multiple clinical and anthropometrical parameters in response to peanut consumption. Meanwhile, the gut microbiota composition is also highly person-specific and have minor changes when compared laterally or longitudinally. This study employs a machine-learning algorithm and establishes prediction models using the microbiome data and the responsiveness data of different parameters in subjects with peanut intervention. As a result, it is found that the improvement of MetS risk and numerous parameters, including diastolic blood pressure, body weight, waist circumference, and fasting blood glucose level can be predicted for responsiveness with high accuracy that has a value of area under curve over 0.70 by receiver operating characteristic analysis. Conclusion Together, the findings of this study suggest that individual gut microbiota configuration may modulate host metabolism and alter an individual's response to peanut intervention, thus highlighting the importance of personalized nutrition.

Dietary interventions such as fasting have been proved to be effective in the prevention of metabolic and autoimmune diseases as well as aging-related conditions. The complicated interaction between nutrition and immunity has drawn wide attention in recent years. In this study, we investigated the therapeutic effect of intermittent caloric restriction on autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, in mice. EAE was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein 35–55 peptide. After the EAE symptoms became obvious at the 4th week post-immunization, the mice were administered with a modified fasting-mimicking diet (FMD) at 1/3 cal of control for 3 days, followed by ad libitum with normal chow for 4 days. A total of two cycles of FMD was applied. Compared with the mice without receiving caloric restriction, the mice using FMD had significant decreases in EAE severity, immune cell infiltration in spinal cord and CNS demyelination. FMD administration also reversed EAE-mediated CNS accumulation of total CD4+ T cells and in particular, IFN-γ-producing CD4+ T cells. Moreover, FMD application elevated the cell proliferation rate in CNS and enhanced expression of brain-derived neurotrophic factor (BDNF) and remyelination markers. In conclusion, our results indicate that intermittent caloric restriction using the modified FMD was effective in the treatment of EAE through ameliorating inflammatory response and promoting recovery of the damaged tissue.

ObjectiveThis study aimed to estimate the cost-effectiveness of direct-acting antivirals (DAAs) among patients with non-genotype 1 for the eradication of hepatitis C virus (HCV) infection in China.MethodsA decision-analytic Markov model was developed to estimate the lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for DAAs and pegylated interferon plus ribavirin (PEG-RBV) from a societal perspective. The model inputs were derived from the literature, a patient survey, HCV expert opinions and a specialised drug price database available in China. Sensitivity analysis was conducted to evaluate the model robustness and calculate reasonable prices of DAAs.ResultsFor patients infected with HCV genotype 2, the pan-genotypic regimen sofosbuvir/velpatasvir (SOF/VEL) was the most cost-effective strategy compared with PEG-RBV, with an ICER of US$5653/QALY. For genotype 3, the combination of sofosbuvir plus daclatasvir (SOF-DCV) was the most cost-effective approach, with an ICER of US$3314/QALY. All DAA regimens for genotype 6 were cost-saving, and sofosbuvir plus ribavirin (SOF-RBV) was the optimal regimen. One-way sensitivity analysis demonstrated that the ICERs were most sensitive to the utility values, discount rate and drug costs. Probabilistic sensitivity analysis indicated that using a threshold equal to one time the gross domestic product (GDP) per capita in China (US$9769/QALY, 2018), the probability of SOF/VEL, SOF-DCV and SOF-RBV being cost-effective was 58%, 83% and 71% for genotype 2, 3 and 6, respectively. Threshold analysis showed that the price of DAAs should be reduced by some degree to achieve better affordability.ConclusionsDAAs were cost-effective compared with traditional treatments. A reasonable reduction in the price of DAAs will increase drug affordability and is of great significance as a global strategy to eradicate viral hepatitis.

Fasting and especially intermittent fasting have been shown to be an effective intervention in many diseases, such as obesity and diabetes. The fasting-mimicking diet (FMD) has recently been found to ameliorate metabolic disorders. To investigate the effect of a new type of low-protein low-carbohydrate FMD on diabetes, we tested an FMD in db/db mice, a genetic model of type 2 diabetes. The diet was administered every other week for a total of 8 weeks. The intermittent FMD normalized blood glucose levels in db/db mice, with significant improvements in insulin sensitivity and β cell function. The FMD also reduced hepatic steatosis in the mice. Deterioration of pancreatic islets and the loss of β cells in the diabetic mice were prevented by the FMD. The expression of β cell progenitor marker Ngn3 was increased by the FMD. In addition, the FMD led to the reconstruction of gut microbiota. Intermittent application of the FMD increased the genera of Parabacteroides and Blautia while reducing Prevotellaceae, Alistipes and Ruminococcaceae. The changes in these bacteria were also correlated with the fasting blood glucose levels of the mice. Furthermore, intermittent FMD was able to reduce fasting blood glucose level and increase β cells in STZ-induced type 1 diabetic mouse model. In conclusion, our study provides evidence that the intermittent application of an FMD is able to effectively intervene in the progression of diabetes in mice. Electronic supplementary material The online version of this article (10.1186/s12986-018-0318-3) contains supplementary material, which is available to authorized users.

Continuous deficiency of leucine, a member of branched chain amino acids, is able to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting has been shown to be effective in intervention of metabolic disorders including diabetes. However, it is unknown whether intermittent leucine deprivation can intervene in type 2 diabetes progression. We administered leucine-deprived food every other day in db/db mice, a type 2 diabetes model, for a total of eight weeks to investigate the interventional effect of intermittent leucine deprivation. Intermittent leucine deprivation significantly reduces hyperglycemia in db/db mice independent of body weight change, together with improvement in glucose tolerance and insulin sensitivity. The total area of pancreatic islets and β cell number are increased by intermittent leucine deprivation, accompanied by elevated proliferation of β cells. The expression level of Ngn3, a β cell progenitor marker, is also increased by leucine-deleted diet. However, leucine deficiency engenders an increase in fat mass and a decrease in lean mass. Lipid accumulation in the liver is elevated and liver function is compromised by leucine deprivation. In addition, leucine deficiency alters the composition of gut microbiota. Leucine deprivation increases the genera of Bacteroides, Alloprevotella, Rikenellaceae while reduces Lachnospiraceae and these changes are correlated with fasting blood glucose levels of the mice. Collectively, our data demonstrated that intermittent leucine deprivation can intervene in the progression of type 2 diabetes in db/db mice. However, leucine deficiency reduces lean mass and aggravates hepatic steatosis in the mouse.

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.

PIP5K1β is crucial to generation of phosphotidylinosotol (4, 5) P2. PIP5K1β participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to make insight into the function of PIP5K1β in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and PIP5K1β was highly expressed both during osteoclast and osteoblast differentiation, besides, PIP5K1β deletion enhanced the proliferation and migration of BMMs to promote osteoclast differentiation. PIP5k1β−/− osteoclast exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1β deficiency also promoted activation of MAPK and Akt signaling, enhanced TRAF6 and c-Fos expression, facilitated the expression and nuclear translocation of NFATC1 and upregulated Grb2 expression, thereby accelerating osteoclast differentiation and function. Finally, PIP5K1β enhanced osteoblast differentiation by upregulating master genes expression through triggering smad1/5/8 signaling. Thereby, PIP5K1β modulate bone homeostasis and remodeling.

Summary: Objective: This study aims to discover that the urinary C-terminal telopeptide of type II collagen (uCTX-II) levels differ between osteoarthritis (OA) patients and healthy individuals (controls). According to this difference, we may conclude that uCTX-II can be a biomarker for OA diagnosis. Methods: We searched MEDLINE and EMBASE databases updated to 2014 to find literature on OA biomarkers. We retrieved the publications that met the required criterion. Literature quality was assessed according to the Newcastle–Ottawa Scale. Publication bias was assessed by Begg's test and Egger's test with the software STATA version 12.0. The weighted mean difference (WMD) was calculated, and the subgroup analysis was completed using STATA 12.0. Results: Six publications were included in our analysis. The WMD for OA patients versus the controls was 83.05, which was within the 95% confidence interval. For subgroup analysis, the WMD of patients with severe OA was 119.92, whereas that of patients with mild OA was 28.07. Conclusions: uCTX-II levels were higher in OA patients than in controls, subgroup analysis revealed that the uCTX-II levels rised with the OA severity, the heterogeneity originated from different levels of OA severity, These results showed that uCTX-II would be a promising clinical biomarker in OA diagnosis. Keywords: biomarkers, osteoarthritis, urinary C-terminal telopeptide of type II collagen

Gas and particle-phase polycyclic aromatic hydrocarbons (PAHs) were measured in air at a background site (Xiaolongmen), two rural village sites (Gubeikou and Donghe), and at an urban site (Beijing) in the North China Plain from September 2007 to August 2008. The annual average total PAH concentration in Donghe was 730.7 ± 608.0 ng/m 3 and 18.2, 3.0, and 1.8 times higher than Xiaolongmen, Gubeikou and Beijing, respectively. Gas/particle partitioning coefficients, K p , were calculated for each PAH and their relationship with the subcooled liquid vapor pressure p 0 l and octanol–air partition coefficients ( K oa ) of the PAHs was investigated. At the rural (Gubeikou) and urban (Beijing) sites, the regression slopes of log K p versus log p 0 l were much steeper than −1, indicating that adsorption of PAHs to particulate matter dominated over absorption possibly because, at these sites, the freshly emitted particulate matter and PAHs had not yet reached equilibrium. However, gas/particle partitioning of PAHs approached equilibrium at the background site (Xiaolongmen) because of long-range transport and longer transport times of the PAHs. In addition, the partitioning between the gas and particle phases was studied according to three different models: the Junge–Pankow adsorption model, the K oa absorption model, and the dual organic matter absorption model combined with the soot carbon adsorption model. The Junge–Pankow model and K oa model both under-predicted our experimental K p values. However, the dual model fit our experimental K p values well. This suggests that PAH adsorption onto soot carbon and absorption into organic matter were both important for PAH gas/particle partitioning in the North China Plain.

Bulk deposition samples were collected in remote, rural village and urban areas of Beijing–Tianjin region, North China in spring, summer, fall and winter from 2007 to 2008. The annually averaged PAHs concentration and deposition flux were 11.81 ± 4.61 μg/g and 5.2 ± 3.89 μg/m2/day respectively. PHE and FLA had the highest deposition flux, accounting for 35.3% and 20.7% of total deposition flux, respectively. More exposure risk from deposition existed in the fall for the local inhabitants. In addition, the PAHs deposition flux in rural villages (3.91 μg/m2/day) and urban areas (8.28 μg/m2/day) was 3.8 and 9.1 times higher than in background area (0.82 μg/m2/day), respectively. This spatial variation of deposition fluxes of PAHs was related to the PAHs emission sources, local population density and air concentration of PAHs, and the PAHs emission sources alone can explain 36%, 49%, 21% and 30% of the spatial variation in spring, summer, fall and winter, respectively.

Five sets of size-fractionated particles were collected in a northern China village in various seasons in order to measure respirable airborne particulates (PM10) and particulate phase polycyclic aromatic hydrocarbons (PAHs) in ambient air. The time-weighted annual mean concentration and standard deviation of PM10 were 358 +/- 107 microg/m3, higher than both the national standard (100 microg/m3) and the levels observed in several contaminated northern Chinese cities. In addition to high levels of PAHs (391 +/- 487 ng/m3), the fraction of higher molecular weight PAHs was higher than most reported in the literature, and the time-weighted annual mean benzo(a)pyrene equivalent concentration was 44.2 +/- 51.4 ng/m3, more than four times the national standard of 10 ng/m3 and 44 times the WHO guideline of 1 ng/m3. Apparently, residents in Donghe suffer from exposure to high levels of both PM10 and particulate phase PAHs. The particle size distribution was centered in the range of Dpor = 3.3 microm in winter and shifted to the ranges of Dpor = 2.1 microm and 5.8 micromDp10 microm in spring and summer respectively. Approximately 90.0% of PAHs were associated with airborne particulates with Dpor = 2.1 microm.

Passive air sampling (PAS) was employed to study the occurrence of gaseous and particle-bound PAHs in the North Chinese Plain. The averaged concentrations of gaseous and particle-bound PAHs were 485+/-209 ng/m(3) and 267+/-161 ng/m(3), respectively. The PAHs concentrations at urban sites were generally higher than those at rural ones with ratios

Cartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and tumor necrosis factor (TNF)-α has critical role in this process by driving inflammatory cascades and cartilage degradation. However, the negative regulation of TNF-α-mediated signaling remains undefined. Here we demonstrate the crucial role of miR-145 in the modulation of TNF-α-mediated signaling and cartilage matrix degradation. MicroRNA (miRNA) expression profiles of TNF-α-stimulated chondrocytes showed that miR-145 expression was rapidly downregulated by TNF-α. Moreover, miR-145 was directly repressed by p65 and was negatively correlated with TNF-α secretion during OA progression. Further, we found that miR-145 directly targeted mitogen-activated protein kinase kinase 4 (MKK4) and broadly restrained the production of several TNF-α-triggered matrix-degrading enzymes (MMP-3, MMP-13, and Adamts-5). Mechanistic studies unveiled that miR-145 negatively regulated TNF-α-mediated JNK and p38 activation, as well as the nuclear accumulation of p-c-Jun and p-ATF2, by inhibiting MKK4 phosphorylation, eventually resulting in the alteration of catabolic genes transcription. Indeed, p-ATF2 interacted with the promoter of Mmp-13, whereas p-c-Jun bound to promoters of Mmp-3 and Adamts-5. MKK4 was significantly elevated in OA cartilage. Eliminating MKK4 by short hairpin RNA resulted in obviously decreased matrix-degrading enzymes production, JNK and p38 inactivation, and an inhibition of cartilage degradation. On the contrary, MKK4 overexpression enhanced TNF-α-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation. Moreover, intra-articular (IA) injection of miR-145 agonist to rat with surgery-induced OA alleviated cartilage destruction. Altogether, we elucidate a novel regulatory mechanism underlying TNF-α-triggered cartilage degradation and demonstrate the potential utility of miR-145 and MKK4 as therapy targets for OA.

The blood–brain barrier (BBB) is a functional structure which regulates and restricts the transfer of circulating molecules and immune cells into the central nervous system. The barrier is formed by the presence of tight junctions (TJ) between the specialized brain endothelial cells. The volatile anesthetic isoflurane may affect the permeability of the BBB. Previous studies have proven that isoflurane alters hypoxia-inducible factor-1α (HIF-1α) expression, which may affect the TJ proteins; however, the mechanism of how TJ proteins are affected by isoflurane is still unclear. Primary human brain vascular endothelial cells (HBVEC) were exposed to isoflurane at various concentrations (0–2.5%) and different time periods (0–6 h). The cell viability, occludin expression, paracellular permeability, VEGF expression, TGF-β3 expression and occludin protein endocytosis were quantified. Isoflurane treatment induced a time- and concentration-dependent decrease in occludin mRNA and protein levels in HBVEC. This effect was partially abrogated by silencing the HIF-1α expression. Isoflurane could activate HIF-1α, and the overexpression HIF-1α up-regulated the level of VEGF and TGF-β3, VEGF decreased the expression of occludin and TGF-β3 accelerated the endocytosis of occludin. RNA interference targeting HIF-1α reduced both VEGF and TGF-β3 expression after isoflurane treatment. Conclusion This study provides direct evidence in vitro that exposing isoflurane to HBVECs can trigger HIF-1α activation, leading to lower protein levels of occludin, and increased permeability of the BBB.

A passive sampler which can be used to collect both gaseous and particulate phase polycyclic aromatic hydrocarbons (PAHs) in air was previously developed and calibrated. The sampler was successfully used in a field study in North China Plain. However, the relatively low uptake rate for particulate phase PAHs prevented it from being applied in nonseverely contaminated environment. The sampler was redesigned to increase the uptake rate for particulate phase PAHs and calibrated in the field for individual PAH compounds of various molecular sizes. The effect of a fine-screen-mesh wrapping on the performance of the sampler was tested. It was found that the sampling efficiencies of the sampler for various PAH compounds were different depending on their molecular weights. For particulate phase PAHs, the uptake rates for high molecular weight compounds, which are favorably associated with fine particles, were generally lower than those for low molecular weight ones. Two calibration equations with molecular weight as an independent variable were developed to predictthe ambient air concentrations of gaseous and particulate phase PAHs based on the results of the passive sampling. The uptake rates of the sampler were different for various PAH compounds. On average, the uptake rates of the sampler for gaseous and particulate phase PAHs were 0.38 +/- 0.51 m3/d and 0.61 +/- 1.41 m3/d, respectively. The latter was 2 orders of magnitude higher than the old model. The sampler was less efficient than active sampler for collecting fine particles in the air and such bias in sampled size distribution can be moderated by a fine-screen-mesh wrapping. However, the wrapping could also reduce the sampling efficiency.

The contamination and outflow of atmospheric polycyclic aromatic hydrocarbons (PAHs) in the Chinese Northern Plain, a region with a total area of 300 000 km2 and a high PAH emission density, were investigated. Polyurethane foam (PUF) and PM10 samples were collected at 46 sites located in urban, rural (towns or villages), and control (remote mountain) areas in the winter from November 2005 to February 2006. The observed concentrations of atmospheric PAHs were generally higher than those reported for developed countries and southern Chinese cities. It was found that there was no significant difference in air PAH concentrations between the urban and the rural areas (514 +/- 563 ng/m3 and 610 +/- 645 ng/ m3, respectively), while the PAH concentrations at the control sites (57.1 +/- 12.6 ng/m3) were 1 order of magnitude lower than those at the other sites. The primary reason for the similarity in PAH concentrations between urban and rural areas was the fact that the predominant sources of biomass and domestic coal combustion were widely spread over the study area. The partition constants (K(PM10)) of PAHs were significantly correlated to the corresponding values of subcooled liquid-vapor pressure (pL0). However, the regression slopes of log K(PM10) versus log pL0 were much steeper than -1, indicating adsorption dominated over absorption. Three distinct patterns of outflow from the study area were identified by forward trajectory and cluster analysis.