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Background Papillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC). Gender is a prominent background parameter for patients with PTC. Here, we aimed to delineate the differences in cell clusters and immune microenvironment in relation to gender in PTC. Methods We generated 6720, 14,666, and 33,373 single-cell transcriptomes that were pooled from the tissues of four male patients with PTC, seven female patients with PTC, and three patients with nodular goiter, respectively. We performed single-cell RNA-sequencing (scRNA-seq) based on BD Rhapsody and characterized the first single-cell transcriptomic landscape of PTC involving gender. The differential cell clusters and their gene profiles were identified and analyzed via a multi-resolution network in male and female patients. The interactions of fibroblasts and endothelial cells with malignant epithelial cells and the difference in the immune infiltration of B and T lymphocytes according to gender were assessed. Results Malignant epithelial cells were divided into two distinct subsets in male and female patients with PTC. Moreover, significant differences involving inferred copy-number variations (CNVs), gene profiles, and cell differentiation were detected between male and female patients. Regarding the interactions of fibroblasts and endothelial cells with malignant epithelial cells, members of the human leukocyte antigen (HLA) family and their receptors were considered as typical in female patients with PTC, while transforming growth factor beta 1 (TGFB1) and its receptors were typical of male patients with PTC. The characteristics of B cells, including cell clusters, cell differentiation, and dominant gene sets, were significantly different between genders. Conclusions Our data revealed the detailed differences in cell clusters and immune microenvironment in PTC according to gender at the single-cell level, which provided new insights into the understanding of the impact of gender on PTC.

Objective: To assess the efficacy and safety of berberine in the treatment of prediabetes. Methods: We searched the following databases, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, Embase, and Medline (OVID) from the databases established to December 2020 in Chinese or English language. Randomized control trials (RCTs) of berberine compared with lifestyle modification, placebo, and/or hypoglycaemics intervention on treating prediabetes were included. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. RevMan 5.4 was used for the meta-analysis. Results: Seven studies involving 859 participants were included in the study and the control groups were all lifestyle modification or metformin treatment. The clinical heterogeneity of the trials was relatively high, and the methodological quality of most trials was generally low. Meta-analysis suggested that berberine could reduce FPG (P = 0.001), 2hPG (P = 0.001) and HbA1c (P = 0.002) levels significantly as compared with lifestyle group. There was no statistical significance between berberine and metformin. No serious adverse effects from berberine were reported. Conclusions: Berberine has good efficacy and safety in the treatment of prediabetes. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.

Objective: To assess the effects of berberine and metformin on glucose in patients with type 2 diabets mellitus (T2DM) with a systematic review and meta-analysis. Methods: The databases including PubMed, Excerpta Medica Database (EMBase), Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI), WanFang, the Chinese Scientific and Technical Journals database (VIP), China Doctor Dissertation Full-text Database (CDFD) and China Master Dissertation Full-text Database (CMFD) from the inception to April 2021 in Chinese or English language were searched. Randomized controlled trials (RCTs) of berberine only or combined with metformin versus metformin were included. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. RevMan 5.4 was used for the meta-analysis. Results: A total of thirteen studies were included, covering 1173 participants. The clinical heterogeneity of the included trials was relatively high. The methodological quality of most trials was generally low with bias in terms of random sequence generation, allocation concealment, blinding method, outcome data and selective reporting. Interventions were divided into two subgroups for analysis. Meta-analysis suggested that there was no statistical significance in the hypoglycemic effect between berberine and metformin for T2DM. However, berberine combined with metformin could reduce fasting plasma glucose (FPG) [MD = −1.49, 95% CI (−2.22, −0.76), P MD = −1.89, 95% CI (−2.94, −0.84), P = 0.0004], glycosylated hemoglobin A1c (HbA1c) [MD = −0.65, 95% CI (−0.91, −0.40), P MD = −0.53, 95% CI (−1.03, −0.03), P = 0.04] levels significantly compared with metformin group. No severe adverse effects were reported in all trials. Conclusions: The hypoglycemic effect of berberine alone is not better than metformin. But berberine combined with metformin has good efficacy and safety in the treatment of T2DM. The current clinical studies are low in methodology and reporting quality, which needs to be further proved by more high quality, large sample size and multi-center RCTs.

Tumour‐associated macrophages (TAMs), which possess M2‐like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI‐251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI‐251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI‐251(rhVEGI‐251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase‐8 and caspase‐3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI‐251‐triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI‐251, activates the JNK pathway via TRAF2 in a potentially DR3‐dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI‐251 that might lead to future development of antitumour therapeutic strategies using VEGI‐251 to target TAMs.

Objective: To observe the clinical efficacy and safety of berberine in treating patients with prediabetes. Methods: A total of 76 patients with prediabetes were enrolled, and at the end of a one-month run-in period, 70 patients were eligible to participate in the clinical trial and randomly assigned to two groups in a 1:1 ratio, namely a treatment group (n = 35) and a control group (n = 35). Members of the control group underwent lifestyle interventions, including dietary interventions and exercise prescriptions, while participants of the treatment group received both lifestyle interventions and oral administration of 300 mg berberine, three times daily for three months. Subsequently, the treatment group entered a washout period of two months, during which time the medication was stopped, and the lifestyle interventions continued. Following the washout period, the oral administration of berberine was resumed at the same dose and lasted for three months. Blood glucose parameters were evaluated after different treatment periods. Results: 1) Intra-group comparison: Following the first and the second treatment periods, the treatment group experienced a significant decrease in fasting plasma glucose (FPG), 2-hour PG (2hPG) based on oral glucose tolerance test (OGTT), HbA1c, and HOMA-IR (P < 0.05); for the control group, although the blood glucose parameters exhibited a downward trend, the differences lacked statistical significance. 2) Intergroup comparison: Compared to the control group, the treatment group showed a signifi-cant decline in the levels of FPG, 2hPG, and HbA1c, whereas the decrease in HOMA-IR had no statistical significance. 3) Safety evaluation: No serious adverse events occurred in either group. Conclusion: Berberine is safe and effective in controlling blood glucose levels in patients with prediabetes and deserves to be promoted in clinical practice.

Background: Type A insulin resistance syndrome is a rare congenital severe insulin resistance syndrome resulting from mutations in the insulin receptor (IR) gene. We herein report a case treated with continuous subcutaneous insulin infusion (CSII) followed by insulin glargine and pioglitazone. Clinical Case: A 16 year-old girl with BMI of 19.1 kg/m2, complained of primary amenorrhea and elevated glucose for 2 years. She was diagnosed with precocious puberty at the age of 7, and treated with letrozole and triptorelin successively for 6.5 years. Hyperinsulinemia was noted but not ameliorated with metformin treatment. All the treatment was suspended for 2 years before referring to our department. Plasma glucose during OGTT showed fasting glucose was 8.4 mmol/L, and 2-hour post-load was 23.5 mmol/L. HbA1c was 10.8%. Markedly increased fasting (245μU/mL) and post-load serum insulin (628μU/mL) were observed. Next generation sequencing revealed a novel heterozygous missense mutation of Trp1120Gly in the IR gene. The patient received CSII with 0.8U/kg as the starting daily total, and titrated the dosage according to SMBG, followed by insulin glargine and pioglitazone treatment. Her glucose was well controlled, insulin glargine was down to 8U/d at the end of 3 months. Her HbA1c dropped to 7.9%, along with fasting plasma glucose (4.6mmol/L) and serum insulin (95.44μU/mL), while 2-hour postprandial glucose and insulin were still high. Her menarche occurred after one cycle of ethinylestradiol and cyproterone combo tablets. Conclusion: Improvement of glucose control with intensive insulin treatment was observed in a patient with type A insulin resistance syndrome. However, amelioration of insulin resistance was limited. No standard treatment was recommended for this rare syndrome. Thus, large-scale long-term studies assembled worldwide to optimize treatment strategy are needed. Disclosure Y. Yang: None. Z. Huang: None. G. Wei: None. Y. Li: None. W. Deng: None. Y. Li: None. Funding National Natural Science Foundation of China (82070918)

Thyroid cancer is the most common endocrine malignancy, and its incidence has increased rapidly in recent decades worldwide. Papillary thyroid cancer (PTC) is the most common type of all thyroid cancers. The molecular mechanisms underlying the disease still need to be further investigated. Long noncoding RNAs (lncRNAs), a class of noncoding RNAs (ncRNAs) longer than 200 nucleotides, are aberrantly expressed in malignant diseases, including PTC. Here, we identified a novel isoform of LOC100129940 and designated it as LOC100129940-N. We demonstrated that the expression level of LOC100129940-N was elevated in PTC, indicating that LOC100129940-N may be involved in PTC development and progression. Moreover, our results showed that overexpression of LOC100129940-N promoted, whereas silencing of LOC100129940-N suppressed, PTC cell proliferation, invasion, and migration. Mechanistically, LOC100129940-N played an important role in activating Wnt/β-catenin signaling and upregulating downstream target genes. Taken together, we demonstrate that LOC100129940-N promotes the activation of Wnt/β-catenin signaling, which in turn regulates the downstream target genes, thereby enhancing invasion and progression of PTC.

The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action. In this work, we focused our investigation on the possible antiviral effect of a novel ISG, C19orf66 in response to ZIKV infection and the associated mechanisms. We found that ZIKV infection could induce C19orf66 expression in ZIKV-permissive cells, and such an overexpression of C19orf66 remarkably suppressed ZIKV replication. Conversely, the depletion of C19orf66 led to a significant increase in viral replication. Furthermore, C19orf66 was found to interact and co-localize with ZIKV nonstructural protein 3 (NS3), thus inducing NS3 degradation via a lysosome-dependent pathway. Taken together, this study identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically degrading a viral nonstructural protein. These findings uncovered an intriguing mechanism of C19orf66 that targeting NS3 protein of ZIKV, providing clues for understanding the actions of innate immunity, and affording the possible availability of new drug targets that can be used for therapeutic intervention., Author summary ZIKV represents a serious threat to global health with particular relevance to microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. Despite the global health threat of Zika virus infection, there is currently no vaccine or effective antiviral therapy available for the disease. As widely recognized, interferon signaling is key to establishing a strong antiviral state in host cells, mainly mediated through the anti-viral effects of numerous interferon-stimulated genes (ISGs). This work described our novel finding of the antiviral effect of a novel ISG, C19orf66, and its underlying mechanisms. We identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically interacting and colocalizing with the ZIKV nonstructural (NS) protein NS3, which inducing NS3 degradation via a lysosome-dependent pathway. Thus, this work broadens the understanding of the pivotal roles of C19orf66 in the interaction between the host and ZIKV, which might further provide a rational basis for developing novel anti-ZIKV strategies.

Hypertriglyceridaemia is a very rare disorder caused by the mutations of LPL gene, with an autosomal recessive mode of inheritance. Here, we identified two unrelated Chinese patients manifested with severe hypertriglyceridaemia and acute pancreatitis. The clinical symptoms of proband 1 are more severe than proband 2. Whole exome sequencing and Sanger sequencing were performed. Functional analysis of the identified mutations has been done. Whole exome sequencing identified two pairs of variants in LPL gene in the proband 1 (c.162C>A and c.1322+1G>A) and proband 2 (c.835C>G and c.1322+1G>A). The substitution (c.162C>A) leads to the formation of a truncated (p.Cys54*) LPL protein. The substitution (c.835C>G) leads to the replacement of leucine to valine (p.Leu279Val). The splice donor site mutation (c.1322+1G>A) leads to the formation of alternative transcripts with the loss of 134 bp in exon 8 of the LPL gene. The proband 1 and his younger son also harbouring a heterozygous variant (c.553G>T; p.Gly185Cys) in APOA5 gene. The relative expression level of the mutated LPL mRNA (c.162C>A, c.835C>G and c.1322+1G>A) showed significant differences compared to wild-type LPL mRNA, suggesting that all these three mutations affect the transcription of LPL mRNA. These three mutations (c.162C>A, c.835C>G and c.1322+1G>A) showed noticeably decreased LPL activity in cell culture medium but not in cell lysates. Here, we identified three mutations in LPL gene which causes severe hypertriglyceridaemia with acute pancreatitis in Chinese patients. We also described the significance of whole exome sequencing for identifying the candidate gene and disease-causing mutation in patients with severe hypertriglyceridaemia and acute pancreatitis.

We discussed how consumers choose eWOM from E-commerce websites and social media.EC-eWOM usefulness and credibility negatively influence the adoption of SM-eWOM.EC-eWOM adoption negatively impacts SM-eWOM adoption.EC-eWOM adoption mediates the relationship between usefulness and SM-eWOM.EC-eWOM adoption mediates the relationship between credibility and SM-eWOM. The influence of user generated content on e-commerce websites and social media has been addressed in both practical and theoretical fields. Since most previous studies focus on either electronic word of mouth (eWOM) from e-commerce websites (EC-eWOM) or social media (SM-eWOM), little is known about the adoption process when consumers are presented EC-eWOM and SM-eWOM simultaneously. We focus on this problem by considering their adoption as an interactive process. It clarifies the mechanism of consumer's adoption for those from the perspective of cognitive cost theory. A conceptual model is proposed about the relationship between the adoptions of the two types of eWOM. The empirical analysis shows that EC-eWOM's usefulness and credibility positively influence the adoption of EC-eWOM, but negatively influence that of SM-eWOM. EC-eWOM adoption negatively impacts SM-eWOM adoption, and mediates the relationship between usefulness, credibility and SM-eWOM adoption. The moderating effects of consumers' cognitive level and degree of involvement are also discussed. This paper further explains the adoption of the two types of eWOM based on the cognitive cost theory and enriches the theoretical research about eWOM in the context of social commerce. Implications for practice, as well as suggestions for future research, are also discussed.

Background: Transmembrane protease serine 4 (TMPRSS4), one of the type II transmembrane serine proteases (TTSPs), is elevated in various cancers and is associated with multiple malignant phenotypes. However, the expression pattern and biologic significance of TMPRSS4 in thyroid cancer are largely unknown. In this study, we investigated the expression of TMPRSS4 in thyroid cancer and assessed the pro-proliferative role of TMPRSS4 in thyroid cancer. Methods: Immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of TMPRSS4 in thyroid cancer. We evaluated in vitro cell proliferation using MTT, colony formation, anchorage-independent growth, flow cytometry analysis, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. Western blot, real-time RT-PCR, and luciferase assays were conducted to reveal the underlying mechanisms. Results: TMPRSS4 is overexpressed in thyroid cancer and is associated with the grade of malignancy. Depletion of TMPRSS4 in thyroid cancer cells significantly suppressed proliferation. Moreover, the proliferation of thyroid cancer cells with TMPRSS4 overexpression was significantly enhanced. We also show that cyclic adenosine monophosphate response element-binding protein (CREB)-cyclin D1 signaling mediates, at least partially, the role of TMPRSS4 in thyroid cancer cell proliferation. Conclusions: TMPRSS4 is overexpressed in thyroid cancer and TMPRSS4-CREB signaling is needed to sustain thyroid cancer cell proliferation.

To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1 cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3.5 mmol/L. Subjects who had received operation were taken into analysis and follow-ups. One hundred and twenty-five patients fulfilled the criteria and were recruited into our research. One hundred and twenty-two operated patients (97.6%) experienced complete resolution of hypokalemia as well as resolution or improvement in hypertension with reduction in antihypertensive medication, while 3 patients (2.4%) failed to obtain normal kalemia and continued on spironolactone therapy. At a median of 65-month (range 21–93) follow-up of these 122 subjects, 27 patients dropped out (22.1%). The 95 responding patients reported no episodes of paralysis or confirmed hypokalemia or any supplementation of potassium. Multivariate linear correlation analysis showed that plasma potassium level was correlated inversely with tumor diameter (r = −0.258, 95% CI −0.076, −0.514, p = 0.037) and basal plasma aldosterone level (r = −0.251, 95% CI −0.040, −0.464, p = 0.042). Most patients with typical unilateral adrenal macroadenomas, normal contralateral glands and hypokalemia could attain favorable surgical therapeutic outcomes without pre-operational AVS lateralization.

Carney complex (CNC) is an extremely rare, multiple endocrine neoplasia syndrome that occurs in an autosomal dominant manner. Mutations in PRKAR1A have been reported to be a common genetic cause of CNC. In this study, we reported a Chinese pedigree of CNC that manifests mainly as spotty skin pigmentation and primary pigmented nodular adrenocortical disease. Whole blood samples of this pedigree were collected for DNA/RNA analysis. Polymerase chain reaction (PCR) and reverse-transcription polymerase chain reaction analyses were performed to amplify the 11 exons and adjacent introns of PRKAR1A. Direct sequencing was used to detect the mutation, and DNA from 70 Han Chinese people was extracted and sequenced as a control to estimate the frequency of the identified mutation. Within the pedigree, ten patients with CNC were identified, and a novel heterozygous mutation (c.440+5 G>C in intron 4a) was identified in the PRKAR1A gene. PCR amplification of cDNA from the control subjects and patients was performed. Agarose gel electrophoresis showed only one wild-type band in the cDNA corresponding to the former group, whereas an extra band was present in samples from the latter group corresponding to the skipping of exon 4a; this confirms that the variant affects PRKAR1A splicing. In conclusion, the c.440+5 G>C mutation is a new splice site mutation that has not been reported and has the potential to broaden the mutational spectrum of PRKAR1A that is associated with CNC, which would facilitate genetic diagnosis and counseling for CNC.

Background Mounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. However, the expression status and functional significance of Trop2 in thyroid cancer are largely unknown. Methods We first determined the expression of Trop2 by using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA) website. The expression of Trop2 was then confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. Cell invasion and migration were assessed by conducting Transwell and wound healing assays. Furthermore, we explored the underlying mechanisms by using real-time RT-PCR, Western blot, zymography, and luciferase reporter assays. Results In this study, we demonstrated that the expression of Trop2 was significantly elevated in thyroid cancer and that its expression level was correlated with the tumor-node-metastasis (TNM) staging and N classification. Dysregulation of Trop2 altered the invasive capability of thyroid cancer cells. Further mechanistic study revealed that MMP2 expression was upregulated by Trop2. Moreover, we found that the effects of Trop2 were dependent on ERK and JNK pathways. The results from clinical specimens showed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer. Conclusion The current study suggests that elevated expression of Trop2 may represent an important molecular hallmark that is biologically and clinically relevant to the progression of thyroid cancer.

A full-scale oxidation ditch process for treating sewage was simulated with the ASM2d model and optimized for minimal cost with acceptable performance in terms of ammonium and phosphorus removal. A unified index was introduced by integrating operational costs (aeration energy and sludge production) with effluent violations for performance evaluation. Scenario analysis showed that, in comparison with the baseline (all of the 9 aerators activated), the strategy of activating 5 aerators could save aeration energy significantly with an ammonium violation below 10%. Sludge discharge scenario analysis showed that a sludge discharge flow of 250-300 m3/day (solid retention time (SRT), 13-15 days) was appropriate for the enhancement of phosphorus removal without excessive sludge production. The proposed optimal control strategy was: activating 5 rotating disks operated with a mode of "111100100" ("1" represents activation and "0" represents inactivation) for aeration and sludge discharge flow of 200 m3/day (SRT, 19 days). Compared with the baseline, this strategy could achieve ammonium violation below 10% and TP violation below 30% with substantial reduction of aeration energy cost (46%) and minimal increment of sludge production (2%). This study provides a useful approach for the optimization of process operation and control.

To explore whether palmitate-induced apoptosis of osteoblastic MC3T3-E1 cell is mediated by an activation of nuclear factor-kappa B (NF-κB).Cell viability was assessed with methyl thiazolyl tetrazolium (MTT) assay and cell apoptosis by Hochest 33258 staining. Palmitate was added at different timepoints and dosages.Western blot was used to evaluate the expression levels of IκBα, p-NF-κB p65 and NF-κB p65 protein.Palmitate led to a dose- and time-dependent decreases in cell viability and increase in cell apoptosis. Cell viability dropped to 54% and cleaved caspase-3 increased 3.1-fold in cells treated with 500 µmol/L palmitate compared to control. The level of p-NF-κB p65 protein markedly increased at 60 min post-stimulation and reached a 2.96-fold increase of baseline level at 120 min (P0.05) . The IκBα level markedly declined at 60 min post-stimulation and decreased by 57% at 120 min (P0.05) . Compared to the group with palmitate treatment alone, pyrrolidine dithiocarbamic acid (10/20 µmol/L) significantly inhibited the palmitate-induced increase of p-NF-κB p65 (1.39 ± 0.12, 1.25 ± 0.10 vs 1.76 ± 0.14, both P0.05) , restored the palmitate-induced decrease of caspase-3 (2.24 ± 0.28 vs 1.29 ± 0.27, P0.05) and inhibited the palmitate-induced increase of cleaved caspase-3 (0.63 ± 0.01 vs 1.13 ± 0.10, P0.05) .Palmitate induces apoptosis of MC3T3-E1 cell by an activation of NF-κB.

Accumulating evidence suggests that some microRNAs (miRNAs) are involved in papillary thyroid carcinoma (PTC) progression. However, it remains necessary to elucidate the underlying molecular mechanisms involved. In the present study, we investigated the role of microRNA-101 (miR-101) in PTC via targeting of Ras-related C3 botulinum toxin substrate 1 (Rac1). The results showed that miR-101 was significantly downregulated in PTC tissues compared with adjacent normal tissues. Restoration of miR-101 expression significantly inhibited cell proliferation in the K1 PTC cell line. Moreover, algorithm-based and experimental strategies verified Rac1 as a direct target of miR-101 in the K1 cell line. Taken together, these findings suggest that miR-101 inhibited PTC growth via the downregulation of Rac1 expression, providing a better understanding of miRNA-modulated signaling networks for future cancer therapeutics.

Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and β-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or α-lipoic acid separately brings about extra benefits.One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with α-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention.The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or α-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P=0.045). The metformin group achieved euglycemia in a shorter time (2.6 ± 1.3 vs. 3.7 ± 1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA β-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with α-lipoic acid was similar to that of CSII alone.Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with α-lipoic acid might not have an additive effect.

In theories and studies of Impulse Buying, residents' impulse buying in Virtual communities (VCs) has been ignored. The purpose of this paper is to provide an explanation of factors influencing impulse buying of Chinese residents in VCs, which can help the advertisers to develop better market strategies. The authors draw on Impulse Buying theories to develop a model of the influence mechanism of users in VCs on the behavioral of impulse buying. The model is tested using data collected among Chinese virtual communities' consumers. The findings illustrate the importance of advertising form, knowledge sharing in a virtual community, the virtual community favorite, impulse buying experiences, users' familiarity and individual instant decision to the residents of virtual communities' impulse buying. The findings of this study have important implications to virtual community or impulse buying researchers. The results of this study also have several important implications for practitioners of advertising in China.

In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age-matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.

To investigate the effects of bezafibrate on the proliferation and differentiation of osteoblastic MC3T3-E1 cells, and to determine the signaling pathway underlying the effects. MC3T3-E1 cells, a mouse osteoblastic cell line, were used. Cell viability and proliferation were examined using MTT assay and colorimetric BrdU incorporation assay, respectively. NO production was evaluated using the Griess reagent. The mRNA expression of ALP, collagen I, osteocalcin, BMP-2, and Runx-2 was measured using real-time PCR. Western blot analysis was used to detect the expression of AMPK and eNOS proteins. Bezafibrate increased the viability and proliferation of MC3T3-E1 cells in a dose- and time-dependent manner. Bezafibrate (100 μmol/L) significantly enhanced osteoblastic mineralization and expression of the differentiation markers ALP, collagen I and osteocalcin. Bezafibrate (100 μmol/L) increased phosphorylation of AMPK and eNOS, which led to an increase of NO production by 4.08-fold, and upregulating BMP-2 and Runx-2 mRNA expression. These effects could be blocked by AMPK inhibitor compound C (5 μmol/L), or the PPARβ inhibitor GSK0660 (0.5 μmol/L), but not by the PPARα inhibitor MK886 (10 μmol/L). Furthermore, GSK0660, compound C, or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mmol/L) could reverse the stimulatory effects of bezafibrate (100 μmol/L) on osteoblast proliferation and differentiation, whereas MK886 only inhibited bezafibrate-induced osteoblast proliferation. Bezafibrate stimulates proliferation and differentiation of MC3T3-E1 cells, mainly via a PPARβ-dependent mechanism. The drug might be beneficial for osteoporosis by promoting bone formation.

Osteoporosis is a bone condition defined by low bone mass and increase of fracture risk due to imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Low bone mass is likely to be due to the alteration of the osteoclast and osteoblast lifespan through regulated apoptosis. Saturated fatty acid (SFA) intake is negatively associated with bone mineral density (BMD). Furthermore, SFA induces apoptosis in osteoblastic cell lines. Bezafibrate could increase bone mass in intact male rats principally through increasing periosteal bone formation. At present, it is unknown whether bezafibrate attenuates palmitate-induced apoptosis in MC3T3-E1 cells. In the present study, we found that palmitate stimulated the degradation of IκBα and NF-κB translocation, as well as up-regulation of NF-κB-mediated Fas expression in obsteoblastic MC3T3-E1 cells. Furthermore, the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) could restore palmitate-induced caspase-3 decrease and inhibit palmitate-induced cleaved caspase-3 increase. We observed that bezafibrate, a dual ligand for the peroxisome proliferator-activated receptors α (PPARα) and PPARδ, significantly attenuated the palmitate-induced cytotoxicity as determined by the MTT assay and inhibited the palmitate-induced apoptosis as determined by a flow cytometry assay using Annexin V-FITC/PI and assessment of the activity of caspase-3. Pre-treatment of bezafibrate prevented palmitate-induced NF-κB activation. Therefore, these findings indicate that bezafibrate inbibits palmitate-induced apoptosis via the NF-κB signaling pathway. Our results point to bezafibrate as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions.

In China, booming tourism is considered to be a win-win solution to fight both ecosystem degradation and poverty in pastoral areas. However, whether this alternative livelihood can reduce pressure on rangeland and improve livelihood of indigenous peoples has not yet been explored. To examine tourism’s impacts on pastoral communities, we conducted field surveys at Inner Mongolia and Xinjiang and distributed questionnaires in 12 provinces including most of the grassland areas of China. On the basis of fieldwork and national survey data, we found that different types of operations have different impacts on livelihood and ecosystem in pastoral area. Pastoralists involved in tourism can increase the income of pastoral households during the summer tourism season, but that pastoralism still provides the main guarantee of a sustainable livelihood. However, along with the development of tourism, business enterprises from outside the pastoral area may replace local herders in tourism operations. As a result, a large area of rangeland may be lost to local herders, who only receive money if they rent their pastures or serve as laborers; unfortunately, many residents lack the training to perform better-paid roles. In addition, we found that pure tourism that replaces pastoralism does not necessarily protect the rangeland, as it brings a variety of environmental impacts and disrupts traditional use that the rangeland may be adapted to. On the basis of our findings, we recommend that tourism managed by local operators who also engage in pastoralism should become the main direction for economic development.

Background and Objectives Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. Design A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. Results Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, −0.10; 95%CI, −0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. Conclusions Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found.