[Mechanism of Xueshuantong Injection on bleomycin-induced pulmonary fibrosis in rats based on coagulation cascade pathway].

This study aims to investigate the mechanism of Xueshuantong Injection(XST) on pulmonary fibrosis induced by bleomycin(BLM) in rats based on the coagulation cascade pathway. Sixty SD rats were randomly divided into sham surgery group,model group, pirfenidone(PFD, 50 mg·kg~(-1)) group, and 27, 54, and 81 mg·kg~(-1) XST groups. The rat model of pulmonary fibrosis was established by intratracheal injection of BLM(5 mg·kg~(-1)). After 24 hours, the administration groups were given corresponding drugs, while the sham surgery group and model group were given equal volumes of saline. On the 28th day, samples were collected,and the imaging and collagen fiber changes in the lungs of rats were observed. Immunofluorescence(IF) method was used to detect the expression level of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col-Ⅰ), E-cadherin(E-cad), and vimentin(Vim). Western blot was used to determine the protein expression of α-SMA, Col-Ⅰ, Vim, and E-cad. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of prothrombin fragment(F1 + 2), thrombin-antithrombin complex(TAT), soluble fibrin monomer complex(SFMC), and rat fibrinogen degradation products(FDP) in rat lung tissue. Finally, the mRNA and protein levels of protease activated receptor 1(PAR-1) were detected by RT-qPCR, western blot, and IF. Compared with the model group, the scanning of the lungs of rats receiving XST treatment also exhibited patchy and non-homogeneous shadows, but these shadows were less dense than those in the model group. At the same time, there was a significant decrease in Col-Ⅰ fibers in the lungs of rats, and XST could inhibit epithelial-mesenchymal transition(EMT) and downregulate α-SMA and Col-Ⅰ protein expression. In the aspect of the coagulation system, administration of 81 mg·kg~(-1) XST significantly reduced the levels of SFMC and FDP. Meanwhile, 81 mg·kg~(-1) XST significantly downregulated the mRNA and protein levels of PAR-1. XST has an anti-pulmonary fibrosis effect in rats, and its mechanism may be related to the downregulation of PAR-1 to rebalance the coagulation cascade pathway.

A General Method to Access Sterically Encumbered Geminal Bis(boronates) via Formal Umpolung Transformation of Terminal Diboron Compounds.

General methods for the preparation of geminal bis(boronates) are of great interest due to their widespread applications in organic synthesis. While the terminal gem-diboron compounds are readily accessible, the construction of the sterically encumbered, internal analogues has remained a prominent challenge. Herein, we report a formal umpolung strategy to access these valuable building blocks. The readily available 1,1-diborylalkanes were first converted into the corresponding α-halogenated derivatives, which then serve as electrophilic components, undergoing a formal substitution with a diverse array of nucleophiles to form a series of C-C, C-O, C-S, and C-N bonds. This protocol features good tolerance to steric hindrance and a wide variety of functional groups and heterocycles. Notably, this strategy can also be extended to the synthesis of diaryl and terminal gem-diboron compounds, therefore providing a general approach to various types of geminal bis(boronates).

A General Strategy for Synthesis of Binary Transition Metal Phosphides Hollow Sandwich Heterostructures.

The hollow sandwich core-shell micro-nanomaterials are widely used in materials, chemistry, and medicine, but their fabrication, particularly for transition metal phosphides (TMPs), remains a great challenge. Herein, a general synthesis strategy is presented for binary TMPs hollow sandwich heterostructures with vertically interconnected nanosheets on the inside and outside surfaces of polyhedron FeCoPx /C, demonstrated by a variety of transition metals (including Co, Fe, Cd, Mn, Cu, Cr, and Ni). Density functional theory (DFT) calculation reveals the process and universal mechanism of layered double hydroxide (LDH) growth on Prussian blue analog (PBA) surface in detail for the first time, which provides the theoretical foundations for feasibility and rationality of the synthesis strategy. This unique structure exhibits a vertical nanosheet-shell-vertical nanosheet configuration combining the advantages of sandwich, hollow and vertical heterostructures, effectively achieving their synergistic effect. As a proof-of-concept of their applications, the CoNiPx @FeCoPx /C@CoNiPx hollow sandwich polyhedron architectures (representative samples) show excellent catalytic performance for the oxygen evolution reaction (OER) in alkaline electrolytes. This work provides a general method for constructing hollow-sandwich micro-nanostructures, which provides more ideas and directions for design of micro-nano materials with special geometric topology.

[Anti-hyperuricemia activity and its mechanism of flavonoid extract from saffron floral bio-residues].

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.

Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis.

Liraglutide is a new hypoglycemic drug. The previous studies have shown that liraglutide can improve the renal outcomes of patients with type 2 diabetes. Recently, it was approved by the U.S. FDA for used as a weight-loss drugs. However, the mechanism of its improvements of renal function in diabetic nephropathy patients is unclear. In addition, the effect of liraglutide on lipid metabolism is also not clear. The purpose of this study was to investigate the effects and mechanisms of liraglutide in alleviating ectopic lipid deposition (ELD) in rats with diabetic nephropathy (DN). Male Sprague-Dawley (SD) rats were treated with high-fat diet + unilateral nephrectomy + low-dose STZ combined to establish a DN rat model to evaluate the lipid-lowering effect of liraglutide. Liraglutide at 0.4 mg/kg/d were subcutaneous injected into for 12 weeks (DN + liraglutide group). After the DN rat model was established, body weight loss, 24-h urine volume increasing, serum triglycerides (TG) and serum total cholesterol (TCh) increasing, ectopic lipid droplet deposition in renal tubular increasing, mesangial proliferation in renal tissue were observed in DN rats. The treatment with liraglutide could reduce the body weight and the average daily food intake of the rats, as well as TG, TCh, and ectopic lipid droplet deposition in renal tubular. Metabolomics result showed that serum differential metabolites between the DN - vehicle control group and the DN + liraglutide group mainly included serine, threonine, phenylalanine, oxyproline, threonine, sorbitol, glyceryl monostearate, glycerol monostearate, and ß-d-glucuronic acid. Moreover, liraglutide can reduce plasma lipid levels in DN rats by increasing the products of lipolysis including 1-monopalmitin and 1-monoostearin. Immunohistochemistry and Western blot showed that the expression levels of lipid synthesis-related sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (FAS) were significantly increased, and lipolysis-related adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were significantly decreased both in the renal tissue of DN rats and PA-induced HK-2 cells (lipid droplet accumulation model). However, liraglutide can attenuate renal tubular ectopic lipid deposition in DN rats by inhibiting SREBP-1, FAS and increasing ATGL, HSL protein expression level, and also ameliorated PA-induced lipid accumulation in renal tubular epithelial cells. These lipid metabolism changes were attributed to liraglutide by upregulating AMP-activated protein kinase (AMPK) phosphorylation in the kidney of DN rats. Collectively, these findings confirm that liraglutide inhibits lipid synthesis and promotes lipolysis to attenuate renal ectopic lipid deposition in DN rats by promoting AMPK phosphorylation.

Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis.

Human ficolin-2 (FCN-2) and mouse ficolin-A (FCN-A, a ficolin-2-like molecule in mouse) are activators of the lectin complement pathway, present in normal plasma and usually associated with infectious diseases, but little is known about the role of FCN-A/2 in inflammatory bowel disease (IBD). In our present study, we found that patients with IBD exhibited much higher serum FCN-2 levels than healthy controls. In the dextran sulphate sodium-induced acute colitis mouse model, FCN-A knockout mice showed much milder disease symptoms with less histological damage, lower expression levels of pro-inflammatory cytokines [interleukin-6 (IL-6), IL-1ß and tumour necrosis factor-α (TNF-α)], chemokines (CXCL1/2/10 and CCL4) and higher levels of the anti-inflammatory cytokine IL-10 compared with wild-type mice. We demonstrated that FCN-A/2 exacerbated the inflammatory pathogenesis of IBD by stimulating M1 polarization through the TLR4/MyD88/MAPK/NF-κB signalling pathway in macrophages. Hence, our data suggest that FCN-A/2 may be used as a novel therapeutic target for IBD.

Assessment of Aphasia Across the International Classification of Functioning, Disability and Health Using an iPad-Based Application.

BACKGROUND: Access2Aphasia™ is an iPad™-based aphasia assessment application that enables real-time audiovisual communication between people with aphasia (PWA) and speech-language pathologists (SLPs), and the use of supported conversation techniques. This study aimed to establish the reliability of aphasia assessment across the International Classification of Functioning, Disability and Health (ICF) using Access2Aphasia, and compare it with face-to-face (FTF) assessment. Consumer perspectives of Access2Aphasia were also examined. MATERIALS AND METHODS: Thirty PWA were randomized into two conditions: online-led and FTF assessment. Participants in the online-led group were assessed remotely using Access2Aphasia™ in their own homes, while an FTF SLP scored silently simultaneously. Participants in the FTF group were assessed FTF using standard administration materials. Assessment included two subtests of the Psycholinguistic Assessment of Language Processing Activities (PALPA) and the Assessment of Living with Aphasia (ALA) to allow for outcomes to be captured across the ICF domains. Consumer perspectives on Access2Aphasia were obtained from both PWA and research SLPs in the online-led group. RESULTS: Kappa statistics indicated moderate to almost perfect agreement between online and FTF SLPs (k = 0.71-1.00). Intrarater and interrater reliability was excellent (ICC = 0.99-1.00) and equivalent for the online-led and FTF conditions. Both PWA and research SLPs in the online-led group reported being satisfied with the experience overall, with suggestions provided by research SLPs to improve Access2Aphasia. CONCLUSION: This study supports the provision of iPad-based aphasia assessments across the ICF in the online environment, with comparable reliability to FTF assessments. Future research is warranted to support the development of iPad-based aphasia assessment and treatment as an alternative mode of service delivery to PWA.

Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis.

BACKGROUND/AIMS: The prognostic value of circulating tumor cells (CTC) detected in hepatocellular carcinoma (HCC) patients is currently under debate. We conducted a meta-analysis of available studies to assess its prognostic value for patients diagnosed with HCC. METHODS: Medline, Ovid Database, Embase, The Science Citation Index, and Cochrane library, search was conducted on all studies reporting the outcomes of interest. The studies were set up according to the inclusion/exclusion criteria. Using a random-effects model, meta-analysis was performed using hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) as effect measures. Heterogeneity of the studies was tested for each pooled analysis. Subgroup and sensitivity analyses were also performed. RESULTS: twenty-three published studies that matched the selection criteria were included in this meta-analysis. CTC positivity was significantly associated with Relapse free survival (RFS) (HR 3.03, 95% CI: [1.89-4.86]; p<0.00001) and Overall survival (OS) (HR 2.45, 95% CI: [1.73-3.48]; p<0.00001). CTC positivity were also significantly associated with TNM Stage (RR 1.30, 95% CI: [1.02-1.65]; p=0.03), Tumor size (RR 1.36, 95% CI: [1.09-1.69]; p=0.006), Vascular invasion (RR 1.99, 95% CI: [1.43-2.77]; p<0.0001), Portal vein tumor thrombus (RR 1.73, 95% CI: [1.42-2.11]; p=0.0001), Serum alpha-fetoprotein (AFP) level (RR 2.05, 95% CI: [1.18-3.54]; p=0.01). CONCLUSION: CTC positivity indicates poor prognosis in patients with hepatocellular carcinoma, and associated with poor clinicopathologic parameters.

Identification and validation of a prognostic anoikis-related gene signature in papillary thyroid carcinoma by integrated analysis of single-cell and bulk RNA-sequencing.

Papillary thyroid carcinoma (PTC) prognosis may be deteriorated due to the metastases, and anoikis palys an essential role in the tumor metastasis. However, the potential effect of anoikis-related genes on the prognosis of PTC was unclear. The mRNA and clinical information were obtained from the cancer genome atlas database. Hub genes were identified and risk model was constructed using Cox regression analysis. Kaplan-Meier (K-M) curve was applied for the survival analysis. Immune infiltration and immune therapy response were calculated using CIBERSORT and TIDE. The identification of cell types and cell interaction was performed by Seurat, SingleR and CellChat packages. GO, KEGG, and GSVA were applied for the enrichment analysis. Protein-protein interaction network was constructed in STRING and Cytoscape. Drug sensitivity was assessed in GSCA. Based on bulk RNA data, we identified 4 anoikis-related risk signatures, which were oncogenes, and constructed a risk model. The enrichment analysis found high risk group was enriched in some immune-related pathways. High risk group had higher infiltration of Tregs, higher TIDE score and lower levels of monocytes and CD8 T cells. Based on scRNA data, we found that 4 hub genes were mainly expressed in monocytes and macrophages, and they interacted with T cells. Hub genes were significantly related to immune escape-related genes. Drug sensitivity analysis suggested that cyclin dependent kinase inhibitor 2A may be a better chemotherapy target. We constructed a risk model which could effectively and steadily predict the prognosis of PTC. We inferred that the immune escape may be involved in the development of PTC.

Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. AIM: To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. METHODS: Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. RESULTS: There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. CONCLUSION: The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Hsa_circ_0001925 promotes malignant progression in triple-negative breast cancer via miR-1299/YY1 axis.

BACKGROUND: Circular RNAs (circRNAs) are related to the pathogenesis and progression of triple-negative breast cancer (TNBC). The aim of this study was to investigate the role and mechanism of hsa_circ_0001925 in TNBC progression. METHODS: Hsa_circ_0001925, microRNA (miR)-1299 and Yin Yang 1 (YY1) levels were examined in TNBC via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, wound healing assay and tube formation assay were conducted to estimate the effects of hsa_circ_0001925 on malignant phenotypes of TNBC tumors. Several protein levels were measured with western blot. The regulatory relationship between miR-1299 and hsa_circ_0001925 or YY1 was validated using a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft assay was used to estimate the effect of hsa_circ_0001925 in TNBC in vivo. RESULTS: Hsa_circ_0001925 and YY1 levels were upregulated, while miR-1299 abundance was downregulated in TNBC tissues and cells. Hsa_circ_0001925 silencing constrained cell proliferation, migration and angiogenesis whereas it promoted apoptosis in vitro, and hsa_circ_0001925 silencing significantly curbed xenograft tumor growth in vivo. Hsa_circ_0001925 acted as a miRNA sponge for miR-1299. Hsa_circ_0001925 decreased YY1 expression by sponging miR-1299. MiR-1299 downregulation alleviated the effects of hsa_circ_0001925 knockdown on BC progression. MiR-1299 interacted with the 3' untranslated region (3' UTR) of YY1, and YY1 overexpression partly reversed the effects of miR-1299 overexpression on BC progression. CONCLUSION: Our findings showed that hsa_circ_0001925 mediated TNBC progression via regulating miR-1299/YY1 axis, providing a potential target for BC treatment.

Malignant form of hidroacanthoma simplex: A case report.

BACKGROUND: This paper presents a case of malignant hidroacanthoma simplex (HAS) and review the literature of previous cases to summarize the histopathological and immunohistochemical features and display the dermoscopic features of malignant HAS. CASE SUMMARY: We present an 88-year-old Asian female with malignant HAS. The diagnosis was made according to the histopathological and immunohistochemical results after biopsy. Previous case reports of malignant HAS were retrieved from PubMed to characterize the histopathological and immunohistochemical features. We also display the dermoscopic features of malignant HAS that have not been reported. CONCLUSION: Our findings demonstrate that prompt surgical treatment is an effective strategy for malignant HAS. Histopathology and immunohistochemistry are valuable diagnostic tools. This is the first case report to display the dermoscopic features of malignant HAS, and we speculate that dermoscopy may contribute to the diagnosis of malignant HAS.

[Effects of Carriers on ANAMMOX Sludge Activity Recovery and Microbial Flora Characteristics].

In order to realize the rapid recovery of ANAMMOX sludge bacterial activity after long-term room temperature storage, three groups of reactors were added to ANAMMOX sludge that had been stored without substrate at room temperature (15-30℃) for 9 months. Among the three groups of reactors, comet fiber carrier and K3 carrier were added to R2 and R3 reactors, respectively, as biological carriers. The effects of different carriers on the recovery rate of ANAMMOX sludge bacterial activity were investigated. The results showed that ANAMMOX reactions in the R2 and R3 reactors began taking place on the 8th and 10th day, respectively, with respective TIN removal rates of 82.25% and 80.92%, which were significantly improved compared with that in the R1 reactor, in which no carrier was added (ANAMMOX reaction started occurring on the 15th day with a TIN removal rate of 80.26%). After 42 days with influent, ρ(NH4+-N) and ρ(NO2--N) respectively increased to 300 mg·L-1 and 396 mg·L-1, and the TIN removal rates of the three groups of reactors were respectively 78.96%, 84.92%, and 84.66%. Microbial community structure analysis showed that the relative abundances of ANAMMOX bacteria in the R2 and R3 reactor were respectively 6.85% and 6.06%, two to four times that in the R1 reactor. The predominant ANAMMOX bacteria in the sludge was Candidatus Jettenia, whose relative abundances in the three groups of reactors were respectively 1.62%, 5.74%, and 5.21%. The results show that ANAMMOX biofilm-granular sludge complex systems constructed by adding carriers can considerably shorten the time for recovering ANAMMOX sludge bacterial activity after long-term room temperature storage without substrate. The carriers effectively promoted the relative abundances of ANAMMOX bacteria in the reactors, whereas the promoting effect of comet fiber carrier was slightly more significant than that of the K3 carrier.

Neuroprotection effects of retained acupuncture in neurotoxin-induced Parkinson's disease mice.

The aim of this study was to investigate the role of retained acupuncture (RA) in neurotoxin-induced Parkinson's disease (PD) mice. Male C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce the PD model. The mice were divided into four groups, namely, (1) normal; (2) MPTP+retained acupuncture (RA); (3) MPTP+electroacupuncture (EA); (4) MPTP+sham acupuncture (SA). After mice being manipulated with/without acupuncture at acupoints (Daling, PC 7), groups 2-4 were injected with MPTP (15 mg/kg/d). The mice were evaluated for behavioral changes, in terms of time of landing, after acupuncture treatment. The animals were sacrificed and their brains assayed for dopamine and its metabolites and tyrosine hydroxylase (TH) expression by using HPLC and immunohistochemistry/Western blotting, respectively. [(123)I] IBZM-SPECT imaging between SA and RA groups were compared. The results showed that the time of landing of the three groups with treatment was significant longer than group 1 (normal) (4.33±0.15 s). Nonetheless, group 2 (RA) (7.13±0.20 s) had a shorter time of landing than group 4 (SA) (7.89±0.46 s). The number of TH (+) neurons and the expression of TH proteins were significantly higher in the RA group than in the SA/EA groups. RA also increased the uptake of [(123)I] IBZM into the triatum compared to the SA group. We conclude that RA possibly attenuates neuronal damage in MPTP-induced PD mice, which suggests RA may be useful as a complementary strategy when treating human PD.

Identification of TNIK as a novel potential drug target in thyroid cancer based on protein druggability prediction.

ABSTRACT: Thyroid cancer is a common endocrine malignancy; however, surgery remains its primary treatment option. A novel targeted drug for the development and application of targeted therapy in thyroid cancer treatment remain underexplored.We obtained RNA sequence data of thyroid cancer from The Cancer Genome Atlas database and identified differentially expressed genes (DEGs). Then, we constructed co-expression network with DEGs and combined it with differentially methylation analysis to screen the key genes in thyroid cancer. PockDrug-Server, an online tool, was applied to predict the druggability of the key genes. Finally, we constructed protein-protein interaction (PPI) network to observe potential targeted drugs for thyroid cancer.We identified 3 genes correlated with altered DNA methylation level and oncogenesis of thyroid cancer. According to the druggable analysis and PPI network, we predicted TRAF2 and NCK-interacting protein kinase (TNIK) sever as the drug targeted for thyroid cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that genes in protein-protein interaction network of TNIK enriched in mitogen-activated protein kinase signaling pathway. For drug repositioning, we identified a targeted drug of genes in PPI network.Our study provides a bioinformatics method for screening drug targets and provides a theoretical basis for thyroid cancer targeted therapy.

Starting from Styrene: A Unified Protocol for Hydrotrifluoromethylation of Diversified Alkenes.

In contrast with unactivated alkenes, the corresponding hydrotrifluoromethylation of styrene has remained challenging due to the strong propensity of styrene for oligomerization and polymerization. On the basis of our newly developed trifluoromethylation reagent, TFSP, herein we present a general method for the hydrotrifluoromethylation of styrene under photoredox catalysis. The substrate scope was further extended to unactivated alkenes, acrylates, acrylamides, and vinyl-heteroatom-substituted alkenes. The tunability of this method was showcased via the relevant deprotonative trifluoromethylation and trifluoromethyltrifluoroethoxylation reactions.

Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer.

BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/ß-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/ß-catenin signaling pathways.

Senile Lemierre syndrome complicated with descending necrotizing mediastinitis: A case report.

RATIONALE: Senile patients with LS complicated with DNM are rarely seen in clinical practice, and extensive cervical incision and drainage plus administration of effective antibiotics are the basis for treatment. Currently, the treatment controversy mainly has focused on whether mediastinal incision and drainage is necessary for patients with type I DNM, and whether anticoagulation therapy is required for jugular venous emboli and distant metastatic emboli induced by LS. PATIENT CONCERNS: A female, 76 years old, developed pain of tonsil on right side 5 days ago, and felt that the pain aggravated complicated with dysphagia and swelling pain of neck on both sides since then. DIAGNOSES: She was diagnosed with LS complicated with type I DNM. INTERVENTIONS: Tazobactam and Piperacillin 4.5 q8h and Ornidazole 100 ml q6h ivgtt were administered empirically,and secondary extensive cervical incision and drainage was performed under general anesthesia, after which low molecular weight heparin 4250 U q12h SC was administered. G test was performed 3 days later, which showed (1,3)-ß-D-glucan >1000 pg/ml. Bridging anticoagulation therapy, low molecular weight heparin 4250 U q12h SC, and Warfarin 2.5 mg qd po were given one week later. Low molecular weight heparin SC was discontinued and only Warfarin po was administered after treatment of bridging therapy for 3 days. OUTCOMES: CT of head and neck was reexamined on post-admission d24 and revealed that neck infection was improved on both sides, jugular vein distension on right side was restored to normal, abscess and pneumatosis of superior mediastinum were improved, distension of pulmonary artery on both sides was normalized, WBC was 9.94×109/L, neutrophil count was 4.43×109/L, CRP level was 9.8mg/L, D-D level was 0.81mg/L, PCT level was 0.800ng/mL and G test suggested (1,3)-ß-D-glucan pf 27.1 pg/mL. LESSONS: Concomitant use of anticoagulants on the basis of repeated cervical incision and drainage + administration of effective antibiotics can obtain excellent therapeutic efficacy in the treatment of patient with LS complicated with type I DNM.