Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

DosR Regulates the Transcription of the Arginine Biosynthesis Gene Cluster by Binding to the Regulatory Sequences in Mycobacterium bovis Bacille Calmette-Guerin.

l-Arginine serves as a carbon and nitrogen source and is critical for Mycobacterium tuberculosis (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the argCJBDFGH gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of argC (rv1652), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in Mycobacterium bovis bacille Calmette-Guerin.

Soil nutrient deficiency decreases the postharvest quality-related metabolite contents of tea (Camellia sinensis (L.) Kuntze) leaves.

The long-term cultivation of tea plants without fertilization can severely decrease yield, but it remains unclear whether this soil nutrient deficiency affects tea quality. In this study, tea plants (Camellia sinensis (L.) Kuntze) cultivated in unfertilized soil for 11 years were analyzed. The soil nutrient deficiency down-regulated protochlorophyllide oxidoreductase-encoding gene expression, which adversely affected chlorophyll biosynthesis, ultimately leading to leaf etiolation. Because of decreased synthesis and increased degradation in response to nutrient deficiency, l-theanine content decreased to 11.4% of the control level, which increased the phenol-ammonia ratio and decreased taste quality. Soil nutrient deficiency also decreased the abundance of many aroma compounds (e.g., green leaf volatile, linalool and its oxides, and methyl salicylate). Thus, nutrient deficiency adversely influences tea color, taste, and aroma. This study provides researchers and tea growers with important information regarding the effects of soil nutrient deficiency on tea quality and the rational fertilization of tea gardens.

The research focus and development trend of art therapy in Chinese education since the 21st century.

Since the 21st century, art therapy has made great progress and development in China's education. To find out the relationship between art therapy and special children, hundreds of related literatures were analyzed using co-word analysis software, which shows that art therapy is increasingly important in special children and their education. Expressive art therapy has a good development prospect in college students' mental health education and group counseling. The connotation of group painting therapy is constantly enriched. The theme research of mandala painting therapy is closely related, and painting art therapy focuses on the psychological counseling research of different groups, but the two are still in the marginal position in the whole research, and have not been paid attention to. Therefore, in the future research, firstly, we should continue to strengthen the research of art therapy and expressive art therapy in special education and individual mental health education; second, further broaden the depth and breadth of group painting therapy; third, strengthen the study of mandala painting therapy and painting art therapy.

Efficacy and safety of ginkgo injections in the treatment of angina pectoris caused by coronary heart disease in China: a network Meta-analysis and systematic review.

OBJECTIVE: To assess the clinical efficacy and safety of ginkgo injections (GIs) combined with conventional treatment (CT) against angina pectoris (AP) due to coronary heart disease (CHD). METHODS: Randomized controlled trials (RCTs) that used GIs to treat AP were searched in SinoMed, PubMed, China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Embase and Cochrane Library until March 2017. The Cochrane"risk of bias"method was used to evaluate the methodological quality of RCTs. Data were analyzed using Stata v13.1 and WinBUGS v1.4.3. RESULTS: A total of 73 RCTs involving 7621 patients were included. A Bayesian network Meta-analysis of RCTs was undertaken, and the advantages of four types of GI-supplemented CT in AP treatment were determined. CONCLUSION: GI-assisted CT was more effective against AP than CT alone. However, based on the limitations of the study, additional high-quality RCTs are required to confirm our findings.

Ginkgo Leaf Extract and Dipyridamole Injection as Adjuvant Treatment for Angina Pectoris: A Meta-Analysis of 41 Randomized Controlled Trials.

OBJECTIVE: To provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection (GD) as one adjuvant therapy for treating angina pectoris (AP) and to evaluate the relevant randomized controlled trials (RCTs) with meta-analysis. METHODS: RCTs concerning AP treated by GD were searched in China Biology Medicine Disc (SinoMed), PubMed, the China National Knowledge Infrastructure Database (CNKI), the Chinese Scientifific Journals Database (VIP), Wanfang Database, Embase, and the Cochrane Library, from inception to February, 2017. The Cochrane Risk Assessment Tool was adopted to assess the methodological quality of the RCTs. The Review Manager 5.3 software was utilized to conduct the meta-analysis. RESULTS: A total of 41 RCTs involving 4,462 patients were included in the meta-analysis. The results indicated that the combined use of GD and Western medicine (WM) against AP was associated with a higher total effective rate [risk ratio (RR)=1.25, 95% confifidence interval (CI): 1.21-1.29, P<0.01], total effective rate of electrocardiogram (RR=1.29, 95% CI: 1.21-1.36, P<0.01). Additional, GD combined with WM could decrease the level of plasma viscosity [mean difference (MD)=-0.56, 95% CI:-0,81 to-0.30, P<0.01], fifibrinogen [MD=-1.02, 95% CI:-1.50 to-0.54, P<0.01], whole blood low shear viscosity [MD=-2.27, 95% CI:-3.04 to-1.49, P<0.01], and whole blood high shear viscosity (MD=-0.90, 95% CI: 1.37 to-0.44, P<0.01). CONCLUSIONS: Comparing with receiving WM only, the combine use of GD and WM was associated with a better curative effect for patients with AP. Nevertheless, limited by the methodological quality of included RCTs more large-sample, multi-center RCTs were needed to confifirm our fifindings and provide further evidence for the clinical utility of GD.

Comparative efficacy of Chinese herbal injections for treating acute cerebral infarction: a network meta-analysis of randomized controlled trials.

BACKGROUND: Chinese herbal injections (CHIs) are prepared by extracting and purifying effective substances from herbs (or decoction pieces) using modern scientific techniques and methods. CHIs combined with aspirin + anticoagulants + dehydrant + neuroprotectant (AADN) are believed to be effective for the treatment of acute cerebral infarction (ACI). However, no randomized controlled trial (RCT) has been performed to directly compare the efficacies of different regimens of CHIs. Therefore, we performed a systematic review and network meta-analysis (NMA) to compare the efficacies of different regimens of CHIs for ACI. METHODS: We conducted an overall and systematic retrieval from literature databases of RCTs focused on the use of CHIs to treat ACI up to June 2016. We used the Cochrane Handbook version 5.1.0 and CONSORT statement to assess the risk of bias. The data were analyzed using STATA 13.0 and WinBUGS 1.4.3 software. RESULTS: Overall, 64 studies with 6225 participants involving 15 CHIs were included in the NMA. In terms of the markedly effective rate, Danhong (DH) + AADN had the highest likelihood of being the best treatment. In terms of the improvement of neurological impairment, Shuxuening (SXN) + AADN had the highest likelihood of being the best treatment. Considering two outcomes, injections of SXN, Yinxingdamo (YXDM), DH, Shuxuetong (SXT), HongHuaHuangSeSu (HHHSS), DengZhanXiXin (DZXX) and Shenxiong glucose (SX) plus AADN were the optimum treatment regimens for ACI, especially SXN + AADN and YXDM + AADN. CONCLUSIONS: Based on the NMA, SXN, YXDM, DH, SXT, HHHSS, DZXX and SX plus AADN showed the highest probability of being the best treatment regimens. Due to the limitations of the present study, our findings should be verified by well-designed RCTs.

Injections of ginkgo in the treatment of cerebral infarction: a systematic review and network Meta-analysis.

OBJECTIVE: To assess the clinical effectiveness and safety of injections of ginkgo (GI) combined with Western Medicine (WM) for cerebral infarction (CI). METHODS: Randomized controlled trials (RCTs) of CI treated by GI were searched in China National Knowledge Infrastructure Database, Wanfang, China Science and Technology Journal Database, Web of Science, Cochrane library, Embase, PubMed and Chinese Biomedical Literature Database, with the publication data no later than April, 2016. The Cochrane risk of bias method was used to evaluate the methodological quality of the RCTs. The data were analyzed by Review Manager 5.3, Stata 13.0, and WinBUGS 14 software. RESULTS: Totally 37 RCTs involving 4330 patients were included. By direct comparison, the results of GI group were significantly superior to the routine WM group in the total effective rates [OR = 3.61, 95% CI (2.93, 4.44), P < 0.0001], the neural function defect score (NFDS) [MD = －4.39, 95% CI (－5.47, －3.32), P < 0.0001]. Network Meta-analysis (NMA) results showed that, between 5 GIs in efficacy, the difference comparing ginaton injections (GbE) to ginkgo-dipyidamolum injections (GD) [OR = 1.74, 95% CI (0.73, 3.65)], shuxuening injections (SXN) [OR = 1.06, 95% CI (0.609, 1.697)] or ginkgolides injections (GK) [OR = 4.711, 95% CI (1.178, 13.21)] reach statistical significance; the difference comparing GD to GK reach statistical significance [OR = 2.791, 95% CI (0.866, 6.908)]; the difference comparing SXN to GK reach statistical significance [OR = 4.537, 95% CI (1.203, 12.41)]. Besides, there was no difference between 4 GIs in NFDS. Probability ranking result showed a great possibility for GK [Surface under the Cumulative Ranking curve (SUCRA) = 80.3%] in improving the total effective rates, which were followed by GD (SUCRA = 73.34%), SXN (SUCRA = 46.59%), GbE (SUCRA = 45.46%), floium ginkgo extract and tertram ethypyrazine sodium chloride injections (FT) (SUCRA = 35.64%). However, GK (SUCRA = 80.3%) or GbE (SUCRA = 69.4%) was better than other GIs in reducing NFDS.GK + WM is the best treatment measures to reduce NFDS in cerebral infarction, which were followed by SXN + WM (SUCRA = 51.6%), GD + WM (SUCRA = 48.1%). CONCLUSION: GIs was more effectiveness on CI than the routine Western Medicine. But based on the limitations of the study, more high-quality randomized controlled trials will be necessary.

New Targets and Cofactors for the Transcription Factor LrpA from Mycobacterium tuberculosis.

Rv3291c (MtbLrpA), a transcriptional regulator, belongs to the leucine-responsive regulatory protein (Lrp) family and is thought to play an important role in Mycobacterium tuberculosis persistence. In this study, we verified 17 novel potential binding sites for MtbLrpA by in vitro binding assays on the basis of previous predictions from an in silico analysis and bacterial one-hybrid (BIH) reporter system. Amino acids, such as tyrosine, phenylalanine, tryptophan, and histidine, strongly affect the binding affinity of MtbLrpA, and vitamins, including B1, B3, B6, VC, B7, B9, B12, VA, and VK3, also decrease MtbLrpA binding affinity. This is the first report regarding that an Lrp-like protein can sense vitamins as an environmental signal. Vitamin supplementation to the environment can change the expression level of the target genes, which provides a potential mechanism for tuberculosis supplementary treatment with vitamins.