Design, synthesis, and biological evaluation of N-(pyridin-3-yl)pyrimidin-4-amine analogues as novel cyclin-dependent kinase 2 inhibitors for cancer therapy.

The discovery and development of CDK2 inhibitors has currently been validated as a hot topic in cancer therapy. Herein, a series of novel N-(pyridin-3-yl)pyrimidin-4-amine derivatives were designed and synthesized as potent CDK2 inhibitors. Among them, the most promising compound 7l presented a broad antiproliferative efficacy toward diverse cancer cells MV4-11, HT-29, MCF-7, and HeLa with IC50 values of 0.83, 2.12, 3.12, and 8.61 µM, respectively, which were comparable to that of Palbociclib and AZD5438. Interestingly, these compounds were less toxic on normal embryonic kidney cells HEK293 with high selectivity index. Further mechanistic studies indicated 7l caused cell cycle arrest and apoptosis on HeLa cells in a concentration-dependent manner. Moreover, 7l manifested potent and similar CDK2/cyclin A2 nhibitory activity to AZD5438 with an IC50 of 64.42 nM. These findings revealed that 7l could serve as ahighly promisingscaffoldfor CDK2 inhibitors as potential anticancer agents and functional probes.

Synthesis and antiproliferative evaluation of novel 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives as potential anticancer agents.

Based on our previous work, a novel class of 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives were synthesized and evaluated as antiproliferative agents. Structure-activity relationship analysis revealed that the greatest activities were achieved with a 4-(4-methylpiperazin-1-yl)aniline group at C-2 position of dihydropteridin-6(5H)-one core, and the most promising compound 6k demonstrated comparable antiproliferative activity with Palbociclib and more potent than our parent derivative 4 toward four cell lines including HCT-116, HeLa, HT-29, and MDA-MB-231 with IC50 values of 3.29, 6.75, 7.56, and 10.30 µM, respectively. Moreover, the mechanism studies revealed that compound 6k could induce cell cycle arrest at G2/M phase via a concentration-dependent manner. In general, these preliminary observations suggested that these compounds could serve as promising scaffolds for further modification to develop novel and highly potent cancer therapy agents.

Development of pteridin-7(8H)-one analogues as highly potent cyclin-dependent kinase 4/6 inhibitors: Synthesis, structure-activity relationship, and biological activity.

CDK4/6 have been validated as the cancer therapeutic targets. Here, we describe a series of pteridin-7(8H)-one analogues as potent CDK4/6 inhibitors. Among them, the most promising compound 7s demonstrated remarkable and broad-spectrum antiproliferative activities toward HCT116, HeLa, MDA-MB-231, and HT-29 cells with IC50 values of 0.65, 0.70, 0.39, and 2.53 µM, respectively, which were more potent than that of the anticancer drug Palbociclib. Interestingly, 7s also manifested the greatest inhibitory activities toward both CDK4/cyclin D3 and CDK6/cyclin D3 (IC50 = 34.0 and 65.1 nM, respectively), which was comparable with Palbociclib. Additionally, molecular simulation indicated that 7s bound efficiently at the ATPbindingsitesofCDK4 and CDK6. Further mechanistic studies revealed that compound 7s could concentration-dependently induce cell cycle arrest and apoptosis in HeLa cells. Takentogether, 7s represents a promising novel CDK4/6 inhibitor for the potential treatment of cancer.

Genome-wide identification of chemosensory receptor genes in the small brown planthopper, Laodelphax striatellus.

The small brown planthopper (SBPH), Laodelphax striatellus is one of the major insect pests of rice, but little is known about the molecular-level means by which it locates its hosts. SBPH host-seeking behavior heavily relies on chemosensory receptors (CRs). In this study, we utilized genome analysis of the SBPH to identify 169 CRs, including: 133 odorant receptors (ORs), 13 gustatory receptors (GRs) and 23 ionotropic receptors (IRs). The phylogenetic relationships of OR genes from three rice planthoppers and other insect species revealed that the odorant co-receptor (Orco) clade is the most conserved group. Among the candidate GRs, two sugar receptors and five fructose receptors have been identified but no carbon dioxide receptors investigated. Furthermore, we identified homologs of the three highly conserved IR co-receptors. The obtained results will provide us with precious information needed to better understand the interaction between insect pests and crop plants required for effective crop protection.

The benefits of expressive writing among newly diagnosed mainland Chinese breast cancer patients.

The study aimed to evaluate the effects of an expressive writing intervention on quality of life (QoL) among mainland Chinese breast cancer patients. A total of 118 Chinese breast cancer patients were randomly assigned to one of four groups: a cancer-facts writing condition (CTL group), an emotional disclosure writing condition (EMO group), a self-regulation writing condition (SR group), or a neutral control condition with no writing tasks (CON group). QoL was assessed by FACT-B at baseline, 3-, and 6-month follow-ups. A repeated measure analysis of variance revealed significant effects of time (F = 13.9, P < 0.001, η2 = 0.20) and the time × group interaction (F = 3.5, P < 0.01, η2 = 0.08) on QoL. Residualized change models showed that the CTL, EMO and SR groups reported higher levels of QoL than the CON group at the 6-month follow-up. The EMO group had a higher level of QoL than the SR group. The CTL group had higher level of physical well-being compared to the SR group. Mainland Chinese breast cancer patients shortly after diagnosis benefit from expressive writing. They benefited more from cancer-facts and emotional disclosure compared to self-regulation. The study indicated that the impact of expressive writing may differ due to stage of cancer survivorship, social, and cultural context.

Molecular characterization and functional analysis of a novel candidate of cuticle carboxylesterase in Spodoptera exigua degradating sex pheromones and plant volatile esters.

Odorant-degrading enzymes (ODEs) are considered to play key roles in odorant inactivation to maintain the odorant receptor sensitivity of insects. Some members of carboxylesterase (CXE) is a major sub-family of ODEs. However, only a few CXEs have been functionally characterized so far. In the present study, we cloned the antennal esterase SexiCXE11 cDNA full-length sequences from the male antennae of a notorious crop pest, Spodoptera exigua, and its encoded 538 amino acids. It was similar to other insect esterases and had the characteristics of a carboxylesterase. We expressed recombinant enzyme in High-Five insect cells and obtained the high level purified recombinant protein by affinity column. Furthermore we test enzyme activity toward its two acetate sex pheromone components (Z9,E12-Tetradecadienyl acetate, Z9E12-14:Ac and Z9-Tetradecenyl acetate, Z9-14:Ac) and other 18 ester plant volatiles. Our results demonstrated that SexiCXE11 degraded acetate sex pheromone components with similar degradation activities (about 15.75% with Z9E12-14:Ac and 19.28% with Z9-14:Ac) and plant volatiles with a relatively high activity such as pentyl acetate and (Z)-3-hexenyl caproate. SexiCXE11 had high hydrolytic activity with these two ester odorants (>50% degradation), which is characterized that although a ubiquitous expression esterase SexiCXE11 may be partly involved with olfaction. This study may facilitate a better understanding of moth ODE differentiation and suggest strategies for the development of new pest behavior inhibitors.

Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation.

OBJECTIVE: To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology. METHODS: Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem and Herbal Ingredients' Targets database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these co-targeted genes were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, and protein-protein interaction (PPI) networks were conducted via the search tool for the retrieval of interacting genes (STRING) database. Cell counting kit-8 (CCK-8) assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes (FLS), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation. RESULTS: Twenty-six co-targeted genes were identified. GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm, and the biological processes mainly involved 'cellular response to hypoxia' 'lipopolysaccharide (LPS)-mediated signaling pathway' and 'positive regulation of gene expression'. KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with 'hypoxia-inducible factor-1 (HIF-1) signaling pathway' and 'tumor-necrosis factor (TNF) signaling pathway'. The PPI network showed that the top 3 hub genes were TP53, TNF, and CASP3. Molecular docking results showed that PF was well docking with TNF. CCK-8 showed no potential toxicity of 10, 20 and 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 ß, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS. CONCLUSION: PF exhibited potent anti-inflammatory effect in OA synovial inflammation.

[Establishment and evaluation of rabbit model of closed tibial fracture].

OBJECTIVE: To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture. METHODS: The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation. RESULTS: Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing. CONCLUSION: The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.

Urea-catalyzed N-Glycosylation of Amides/Azacycles with Glycosyl Halides.

The efficient synthesis of N-glycosides via direct N-glycosylation of amides/azacycles has been reported. The glycosylation of amides/azacycles with glycosyl halides in the presence of a catalytic amount of urea proceeded smoothly to provide the corresponding N-glycosylated amides or nucleosides in good to excellent yields with 1,2-trans-stereoselectivity. Moreover, by the addition of terpyridine, the 1,2-cis-stereoselectivity was achieved.

Targeted delivery of insoluble cargo (paclitaxel) by PEGylated chitosan nanoparticles grafted with Arg-Gly-Asp (RGD).

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, we developed a tumor-targeting delivery system for insoluble drug (paclitaxel, PTX) by PEGylated O-carboxymethyl-chitosan (CMC) nanoparticles grafted with cyclic Arg-Gly-Asp (RGD) peptide. To improve the loading efficiency (LE), we combined O/W/O double emulsion method with temperature-programmed solidification technique and controlled PTX within the matrix network as in situ nanocrystallite form. Furthermore, these CMC nanoparticles were PEGylated, which could reduce recognition by the reticuloendothelial system (RES) and prolong the circulation time in blood. In addition, further graft of cyclic RGD peptide at the terminal of PEG chain endowed these nanoparticles with higher affinity to in vitro Lewis lung carcinoma (LLC) cells and in vivo tumor tissue. These outstanding properties enabled as-designed nanodevice to exhibit a greater tumor growth inhibition effect and much lower side effects over the commercial formulation Taxol.

Toll-Like Receptor 9 Signaling Pathway Contributes to Intestinal Mucosal Barrier Injury in Mice With Severe Acute Pancreatitis.

OBJECTIVES: The purpose of this study was to investigate the role and mechanism of toll-like receptor 9 (TLR9) in intestinal mucosal barrier injury in mice with severe acute pancreatitis (SAP). METHODS: The mice were randomly divided into 3 groups: control group, SAP group, and TLR9 antagonist-treated group. The expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6, diamine oxidase, and endotoxin core antibodies were detected by enzyme-linked immunosorbent assay. The protein expression of zonula occluden-1 (ZO)-1, occludin, TLR9, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), p-nuclear factor (NF)-κB p65, and NF-κB p65 were detected by Western blot. TdT-mediated dUTP nick-end labeling staining was used for detecting intestinal epithelial cell apoptosis. RESULTS: The expression of TLR9 and its related pathway proteins MyD88, TRAF6, and p-NF-κB p65 in the intestinal tract of SAP mice were significantly increased compared with that of control mice. Inhibition of the TLR9 expression could reduce the level of serum proinflammatory cytokines, reduce the apoptosis of intestinal epithelial cells, improve intestinal permeability, and ultimately reduce the damage of intestinal mucosal barrier function in SAP. CONCLUSIONS: Toll-like receptor 9/MyD88/TRAF6/NF-κB signaling pathway plays an important role in intestinal mucosal barrier injury of SAP.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine in Treating Gouty Arthritis: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gouty arthritis is a common metabolic disease caused by long-term purine metabolism and elevated serum uric acid. In recent years, the incidence of gouty arthritis has been increasing year by year. As an effective method for treating gouty arthritis, acupuncture combined with herbal medicine has been widely used in clinical practice. However, the evidence for the treatment needs to be evaluated through systematic review and meta-analysis. Methods. The Cochrane Library, PubMed, Web of Science, EMBASE, China CBM database, Clinical Trials, CNKI, China Wanfang database, and VIP information database were searched from the establishment of each database to March 2021. Randomized controlled trials (RCTs) were included in the study, and the therapeutic effects of acupuncture combined with herbal medicine versus conventional therapy, or acupuncture combined with herbal medicine versus anti-inflammatory drugs, or acupuncture combined with herbal medicine versus acupuncture/herbal medicine alone were compared in the subjects with gouty arthritis. Two authors screened all references, assessed the risk of bias, and independently extracted the data. The binary outcome was summarized using 95% confidence intervals (CIs) and risk ratios (RRs). The overall quality of the evidence was assessed with hierarchy, and meta-analysis was performed with a random-effects model. RESULTS: A total of 14 randomized controlled trials (1,065 participants, 540 treatment groups, and 525 control groups) with treatment courses of 5 to 21 days were included. Acupuncture combined with herbal medicine and acupuncture was compared in three trials, acupuncture combined with herbal medicine and conventional therapy was compared in 14 of them, and acupuncture combined with herbal medicine and anti-inflammatory drugs was compared in 8 of them. The clinical efficacy (clinical symptoms, serological tests, and visual analogue scale (VAS) results) was significantly improved in the acupuncture combined with herbal medicine treatment group (P=0.0005, 95% CI 0.03 to 0.13; 687 participants; 8 trials), and the efficacy in reducing uric acid was also better (P < 0.00001; 95% CI -102.89, -68.37; 100 participants; 2 trials; evidence with moderate quality). The effect of acupuncture combined with herbal medicine was better than that of acupuncture alone (RR 1.22, 95%CI 1.06 to 1.41; 139 participants; 3 trials), the effect of acupuncture combined with herbal medicine was better than that of herbal medicine alone (RR 1.31 95%CI 1.08 to 1.57, 100 participants, 2 trials, evidence with moderate quality), and the effect of acupuncture combined with herbal medicine was better than that of colchicine (P = 0.02, RR 1.14 95%CI 1.02 to 1.27, 2 trials, evidence with moderate quality). The incidence of adverse events was considerably different between the two groups, and the acupuncture combined with herbal medicine group was significantly superior to the control group in terms of adverse events (P < 0.00001; 95% CI (0.08 to 0.32)). CONCLUSIONS: The efficacy of acupuncture combined with herbal medicine was better than conventional drug therapy in treating gouty arthritis. The study results must be interpreted with caution due to the high or unclear risk of bias of the trials included in the study. PROSPERO registration number: CRD42020202544. INPLASY registration number: 202090006.

Responses of phytoliths in topsoil samples to temperature variation in temperate region.

Modern phytolith research is the premise to accurately reconstruct the regional paleovegetation and paleoclimate. It is thus particularly important to study the spatial distribution characteristics of the phytolith assemblages and the response of the phytolith to environmental factors. In this study, we collected 54 topsoil samples along the isohyet of 600 mm in Northeast China to examine the distribution patterns of phytolith along the gradient of single environmental factor. With this special sampling method, we targeted to reveal the responses of phytolith assemblages in the topsoil to the variation of temperature. The results showed that there were a large number of phytoliths with various morphotypes in the 54 topsoil samples in Northeast China. The phytolith morphotypes were the same, including elongate, lanceolate, blocky, cuneiform, tabular, saddle, rondel, bilobate, trapeziform polylobate, prism, silicified stomata, conduit, papillae, sclereid and carinate. In gene-ral, the contributions of elongate and lanceolate were high; the contributions of short cell phytoliths, blocky, tabular and cuneiform were small relatively; the contributions of the other types of phytoliths were less than 1.0% and appeared sporadically in the topsoil samples. Besides, the phytolith assemblages of the topsoil samples were different among Xiaoxing'an Mountains, Songliao Plain and Liaoxi hills. Combined with the discriminant analysis, the samples from the three regions could be effectively separated based on the phytoliths assemblages, with a total accuracy of 94.4%. Specifi-cally, the average percentage of elongate, lanceolate, prism was the largest in Xiaoxing'an Mountains, and was the smallest in Liaoxi hills; the percentage of saddle, bilobate, papillae was the largest in Liaoxi hills and the smallest in Xiaoxing'an Mountains; the percentage of blocky, tabular, cuneiform was the largest in Songliao Plain. Meanwhile, the percentages of the elongate, lanceolate, prism, saddle, bilobate, papillae, blocky, tabular, cuneiform were significant diffe-rences among the three regions. There were significant negative correlations between the percentages of elongate, lanceolate, prism and the annual average temperature, and positive relationships between the percentages of the blocky, tabular, cuneiform, bilobate, papillae and the annual average temperature. However, the percentage of saddle, rondel and trapeziform polylobate did not change with increasing annual average temperature.

Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine.

Gouty arthritis (GA) is a multifactorial disease whose pathogenesis is utterly complex, and the current clinical treatment methods cannot wholly prevent GA development. Western medicine is the primary treatment strategy for gouty arthritis, but it owns an unfavorable prognosis. Therefore, the prevention and treatment of GA are essential. In China, traditional Chinese medicine (TCM) has been adopted for GA prevention and treatment for thousands of years. Gout patients are usually treated with TCM according to their different conditions, and long-term results can be achieved by improving their physical condition. And TCM has been proved to be an effective method to treat gout in modern China. Nevertheless, the pharmacological mechanism of TCM for gout is still unclear, which limits its spread. The theory of prevention and treatment of gout with TCM is more well acknowledged in China than in abroad. In this article, Chinese herbs and ancient formula for gout were summarized first. A total of more than 570 studies published from 2004 to June 2021 in PubMed, Medline, CNKI, VIP, Web of Science databases and Chinese Pharmacopoeia and traditional Chinese books were searched; the current status of TCM in the treatment of GA was summarized from the following aspects: articular chondrocyte apoptosis inhibition, antioxidative stress response, inflammatory cytokine levels regulation, uric acid excretion promotion, immune function regulation, uric acid reduction, and intestinal flora improvement in subjects with gout. The literature review concluded that TCM has a specific curative effect on the prevention and treatment of GA, particularly when combined with modern medical approaches. However, lacking a uniform definition of GA syndrome differentiation and the support of evidence-based medicine in clinical practice have provoked considerable concern in previous studies, which needs to be addressed in future research.

Gua sha therapy for chronic low back pain: A protocol for systematic review.

BACKGROUND: Non-specific chronic low back pain (LBP) is a debilitating disease that profoundly impacts patients' daily physical function and quality of life. Gua sha therapy, as an easy-to-use and noninvasive complementary modality, has been widely used clinically in patients with non-specific chronic LBP. The aim of this study is to test the potential benefits and harms of gua sha therapy on patients with non-specific chronic LBP. METHODS: Ten English databases, 3 Korean databases, 6 Chinese databases, 1 Japanese database, and 2 Brazilian databases will be searched from their inception to September 2019. Randomized controlled trials will be included if gua sha therapy was used as the sole treatment or as a part of combination therapy with other treatments in patients with non-specific chronic LBP. Two reviewers will independently extract the data and assess the methodological quality using the Cochrane criteria for risk of bias. The meta-analysis will be performed using Review Manager 5.3 software. RESULTS: The findings of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide more evidence regarding the clinical usage of gua sha therapy for non-specific chronic LBP. TRIAL REGISTRATION NUMBER: CRD42019134567.

[Effect of Tongluo Zhitong (, TLZT) gel preparation on p53 /miR-502-5p /NF-κBp65 in synovial tissue of knee osteoarthritis].

OBJECTIVE: To observe effects of Tongluo Zhitong (, TLZT) gel preparation on p53, miR-502-5p, NF-κBp65 in synovial tissue of knee osteoarthritis (KOA), and to explore mechanism of TLZT gel preparation in treating KOA. METHODS: Thirthy-six Wistar rats aged 8 weeks and weighed 200 to 220 g (meaned 208 g) were randomly divided into normal group, model group and traditional Chinese medicine (TCM) group, 12 rats in each group. KOA model was established by modified Hulth method. After 4 weeks of modeling, TCM group treated with TLZT gel preparation for external use, 3 times daily for 2 weeks;normal group and model group were fed normally without intervention. After treatment, morphological changes of specimens in each group were observed, changes of miR-502-5p in synovial tissue were detected by qPCR, and contents of p53, NF-κBp65, IL-1ß, TNF-α, MMP-13 in synovial tissue were detected by qPCR and Western Blot respectively. RESULTS: (1)Morphological observation of specimens showed that the articular cartilage in model group was hyaline and uneven, the synovial membranes were hypertrophic and proliferative with a large number of inflammatory cells infiltrating, the joint fluid was thicker in texture;the articular cartilage in TCM group was more transparent and smooth, synovial hyperplasia was mild with a small amount of inflammatory cell infiltration, the texture of articular fluid was clear and sparse. (2) Compared with normal group, content of miR-502-5p of synovial tissue in model and TCM group were increased, mRNA and expression of p53 decreased, expression of NF-κBp65, IL-1ß, TNF-α, MMP-13 increased. (3)Compared with model group, content of miR-502-5p in synovial tissue of TCM group decreased (P<0.05), mRNA and protein expression of p53 increased (P<0.05), mRNA and protein expression of NF-κBp65, IL-1ß, TNF-α, MMP-13 decreased (P<0.05). CONCLUSION: Expression of p53, miR-502 -5p, NF -κBp65 in synovial tissue is closely related to synovial hyperplasia and inflammatory reaction, TLZT gel preparation may reduce proliferation and inflammatory reaction of KOA synovium by regulating the expression of p53, miR- 502-5p, NF-κBp65 in synovial tissues.

The impact of hydrochloric acid on the catalytic destruction behavior of 1,2-dichlorbenzene and PCDD/Fs in the presence of VWTi catalysts.

Catalytic oxidation is regarded an effective technique to control the emissions of chlorinated benzenes (CBzs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from waste incinerators. Among the numerous factors affecting the degradation efficiency of CBzs and PCDD/Fs, limited attention has been paid to the impact of hydrochloric acid (HCl) present in the flue gas. This study investigates how HCl affects the catalytic degradation of 1,2-dichlorbenzene (1,2-DCBz) at different reaction times and temperature regimes. The results showed that the removal efficiency of 1,2-DCBz, which was achieved by the V2O5/WO3-TiO2 (VWTi) catalyst, decreased the largest by 10% in the presence of HCl. Furthermore, it was found that the increasing concentration of water vapor hindered the degradation efficiency of 1,2-DCBz. No relationship between the process temperature and the destruction efficiency of PCDD/Fs was observed in the presence of HCl. Potential increasing of the removal efficiency of 1,2-DCBz was confirmed by adding different amount of activated carbon (AC) in the presence of HCl.

[Lapidus operation combined with bone setting manipulation in treatment of hallux valgus in elderly patients].

OBJECTIVE: To investigate the clinical effect of Lapidus operation combined with bone setting manipulation of traditional Chinese medicine in treating hallux valgus in elderly patients. METHODS: From March 2013 to October 2017, 53 elderly patients (87 feet) with hallux valgus were treated with Lapidus operation combined with bone-setting manipulation of traditional Chinese medicine, including 12 males (18 feet) and 41 females (69 feet), ranging in age from 65 to 92 years old, with an average of (76.3±4.8) years old. Visual analogue scale(VAS) was used to evaluate the degree of relief of foot pain before and 26 months after operation. American Orthopaedic Foot and Ankle Society(AOFAS) was used to evaluate the function of foot pain. The changes of hallux valgus angle(HVA angle), interphalangeal angle (IMA angle) and metatarsal wedge angle(MCA angle) were compared on X-ray films. RESULTS: All the patients were followed up, and the duration ranged from 12 to 42 months, with an average of(26.0±2.7) months. In all patients, the first metatarsal joint reached bone fusion within 6 to 8 months, with an average of 4.7 months. The preoperative VAS score was 8.06±1.44, which was significantly different from 2.14±1.98 at 26 months(P<0.05). The preoperative AOFAS score was 53.90±7.89, which was significantly different from 92.80±2.78 at 26 months(P<0.05). The HVA, IMA and MCA were significantly improved from preoperative(38.60±2.72)°, (21.90±1.91)° and(20.90±2.20)° to the latest follow-up(17.80±1.94)°, (9.70±2.56)° and(11.70±0.48)°(P<0.05). According AOFAS score, 74 feet got an excellent result, 11 good and 2 fair. CONCLUSIONS: Lapidus operation combined with bone-setting manipulation of traditional Chinese medicine on the treatment of hallux valgus foot in elderly patients has satisfactory clinical effects, shortens the time of osteotomy and fixation, protects the soft tissue around the osteotomy end and promotes the bone fusion on the most satisfactory position.

Synthesis and biological evaluation of novel indole-pyrimidine hybrids bearing morpholine and thiomorpholine moieties.

Based on our previous screening hit compound 1, a series of novel indole-pyrimidine hybrids possessing morpholine or thiomorpholine moiety were synthesized via an efficient one-pot multistep synthetic method. The antiproliferative activities of the synthesized compounds were evaluated in vitro against four cancer cell lines including HeLa, MDA-MB-231, MCF-7, and HCT116. The results revealed that most compounds possessed moderate to excellent potency. The IC50 values of the most promising compound 15 are 0.29, 4.04, and 9.48 µM against MCF-7, HeLa, and HCT116 cell lines, respectively, which are 48.0, 4.9, and 1.8 folds more active than the lead compound 1. Moreover, fluorescence-activated cell sorting analysis revealed that compound 14 showing the highest activity against HeLa (IC50 = 2.51 µM) displayed a significant effect on G2/M cell-cycle arrest in a concentration-dependent manner in HeLa cell line. In addition, representative nine active hybrids were evaluated for tubulin polymerization inhibitory activities, and compound 15 exhibited the most potent anti-tubulin activity showing 42% inhibition at 10 µM. These preliminary results encourage a further investigation on indole-pyrimidine hybrids for the development of potent anticancer agents that inhibit tubulin polymerization.

[Progress on establishment of animal model of osteoarthritis by intra-articular injection].

Osteoarthritis (Osteoarthritis, OA) is a common clinical degenerative joint disease with increased incidence rate in recent years. Animal experiment is one of the important ways to explore pathogenesis and treatment of OA, while induced animal model is the most important part in animal experiment. Intra-articular injection of drugs is a classical method for establishing animal model of OA. Choose of animal should follows the principle of correlation, appropriateness and practicability, injections should perform in accordance with experimental purposes and subject, detections means and evaluation methods also should corresponding to experimental reality. The gold standard of OA animal model and intra-articular injections has not build, need further study.