Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Alarmin IL-33 orchestrates antitumoral T cell responses to enhance sensitivity to 5-fluorouracil in colorectal cancer.

Rationale: Resistance to 5-fluorouracil (5-FU) chemotherapy remains the main barrier to effective clinical outcomes for patients with colorectal cancer (CRC). A better understanding of the detailed mechanisms underlying 5-FU resistance is needed to increase survival. Interleukin (IL)-33 is a newly discovered alarmin-like molecule that exerts pro- and anti-tumorigenic effects in various cancers. However, the precise role of IL-33 in CRC progression, as well as in the development of 5-FU resistance, remains unclear. Methods: High-quality RNA-sequencing analyses were performed on matched samples from patients with 5-FU-sensitive and 5-FU-resistant CRC. The clinical and biological significance of IL-33, including its effects on both T cells and tumor cells, as well as its relationship with 5-FU chemotherapeutic activity were examined in ex vivo, in vitro and in vivo models of CRC. The molecular mechanisms underlying these processes were explored. Results: IL-33 expressed by tumor cells was a dominant mediator of antitumoral immunity in 5-FU-sensitive patients with CRC. By binding to its ST2 receptor, IL-33 triggered CD4+ (Th1 and Th2) and CD8+ T cell responses by activating annexin A1 downstream signaling cascades. Mechanistically, IL-33 enhanced the sensitivity of CRC cells to 5-FU only in the presence of T cells, which led to the activation of both tumor cell-intrinsic apoptotic and immune killing-related signals, thereby synergizing with 5-FU to induce apoptosis of CRC cells. Moreover, injured CRC cells released more IL-33 and the T cell chemokines CXCL10 and CXCL13, forming a positive feedback loop to further augment T cell responses. Conclusions: Our results identified a previously unrecognized connection between IL-33 and enhanced sensitivity to 5-FU. IL-33 created an immune-active tumor microenvironment by orchestrating antitumoral T cell responses. Thus, IL-33 is a potential predictive biomarker for 5-FU chemosensitivity and favorable prognosis and has potential as a promising adjuvant immunotherapy to improve the clinical benefits of 5-FU-based therapies in the treatment of CRC.

UPLC-Q-TOF-MS/MS Analysis of Phenolic Compounds from the Fruit of Cephalostachyum fuchsianum Gamble and Their Antioxidant and Cytoprotective Activities.

Bamboo is a widely distributed graminaceous plant in China and is a potential source of bioactive substances. Incidentally, bamboo's fruit is rich in phytochemicals such as polyphenols and flavonoids, which are significant to human health. In this study, we identified the phenolic compounds of the fruit and investigated the antioxidant activities of Cephalostachyum fuchsianum Gamble (CFG) fruit polyphenols with in vitro and in vivo tests for the first time. UPLC-Q-TOF-MS/MS analysis results showed that the fruit contained 43 phenolic compounds, including 7 hydroxybenzoic acids, 12 flavonoids, 7 coumarins, 10 hydroxycinnamic acids, 1 terpenoid, and 5 lignans. The TPC of SP extracts was higher than that of IBPs extracts in FP and FF. The SP extracts in FP showed better antioxidant activities in vitro compared to those in FF. In addition, polyphenols from CFG fruits protected against H2O2-induced oxidative damage in HepG2 cells, and the protective effect of polyphenols in FP was superior to that in FF. The analysis results showed that CFG fruit has great potential in exploiting natural chemical substances, which can provide valuable pieces of information for the further development and utilization of CFG.

Effects of vegetation and terrain changes on spatial heterogeneity of soil C-N-P in the coastal zone protected forests at northern China.

Soil organic carbon (SOC), total nitrogen (TN) and total phosphorus (TP) are important indicators reflecting soil quality, and they can be used to effectively evaluate the effect of soil remediation. Many studies have evaluated the content of SOC, TN and TP in different ecosystems. However, after constructing protected forests for ecological restoration in the ecologically fragile coastal zone, the spatial distribution and influencing mechanism of SOC, TN and TP content is still uncertain. In this study, the spatial heterogeneity and influencing factors of SOC, TN and TP in surface (0-20 cm) soil were analyzed by traditional analysis and geostatistics. A total of 39 soil samples were collected under the coastal zone protected forest types including Quercus acutissima Carruth (QAC), Pinus thunbergii Parl (PTP), mixed PTP and QAC (QP) and Castanea mollissima BL (CMB) in the coastal zone protected forests in northern China. The results show that SOC, TN and TP content were defined as moderate variation, and they also show significant changes under different protected forest types (P < 0.05). The semivariance results indicate that SOC, TN and TP all exhibited strong spatial dependence class, with Range of 224 m, 229 m and 282 m respectively, which were more than the sampling scale of 200 m. The spatial prediction results showed that SOC, TN and TP content all appear in large areas of extremely low value in CMB, and its cross validation results showed that using vegetation and terrain factors as covariates in the spatial prediction of SOC, TN and TP can improve the prediction accuracy. The results of correlation analysis showed that the influencing factor for SOC and TN, and TP were NDVI and topographical changes, respectively. In general, vegetation and terrain factors as auxiliary factors can improved the accuracy of soil C-N-P spatial distribution prediction after afforestation in coastal zone.

Nanophysical Antimicrobial Strategies: A Rational Deployment of Nanomaterials and Physical Stimulations in Combating Bacterial Infections.

The emergence of bacterial resistance due to the evolution of microbes under antibiotic selection pressure, and their ability to form biofilm, has necessitated the development of alternative antimicrobial therapeutics. Physical stimulation, as a powerful antimicrobial method to disrupt microbial structure, has been widely used in food and industrial sterilization. With advances in nanotechnology, nanophysical antimicrobial strategies (NPAS) have provided unprecedented opportunities to treat antibiotic-resistant infections, via a combination of nanomaterials and physical stimulations. In this review, NPAS are categorized according to the modes of their physical stimulation, which include mechanical, optical, magnetic, acoustic, and electrical signals. The biomedical applications of NPAS in combating bacterial infections are systematically introduced, with a focus on their design and antimicrobial mechanisms. Current challenges and further perspectives of NPAS in the clinical treatment of bacterial infections are also summarized and discussed to highlight their potential use in clinical settings. The authors hope that this review will attract more researchers to further advance the promising field of NPAS, and provide new insights for designing powerful strategies to combat bacterial resistance.

Discovery and Nanosized Preparations of (S,R)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.

Effect of in vitro gastrointestinal digestion on phenolic compounds and antioxidant properties of soluble and insoluble dietary fibers derived from hulless barley.

In this study, the bioaccessibility and antioxidant activity of phenolic compounds in insoluble dietary fiber (IDF) and soluble dietary fiber (SDF) derived from hulless barley were evaluated by an in vitro gastrointestinal (GI) digestion model. The total phenolic and flavonoid contents, as well as antioxidant activity of phenolic compounds in IDF and SDF following GI digestion were studied. The results obtained showed an increase in total phenolic and flavonoid contents, as well antioxidant activity compared with undigested extracts. Moreover, the bioaccessibility indexes of phenolic compounds in IDF and SDF were 490.90 ± 3.10% and 1608.79 ± 40.63% respectively, after GI digestion. Similarly, the bioaccessibility indexes of flavonoids in IDF and SDF were 179.20 ± 15.16% and 814.36 ± 26.31%, respectively. Based on our findings, individual phenolic compounds show different stability in the digestion process. The content of ferulic acid has different trends in IDF and SDF during GI digestion. This study could provide a scientific basis for hulless barley DF as valuable food additives. PRACTICAL APPLICATION: Hulless barley is a unique cereal with potential health benefits due to high dietary fiber (DF) content and phenolic compounds. Phenolic compounds could be linked to DF through chemical bonds. Phenolic compounds in DF can be slowly and continuously released under acidic, alkaline, and enzymatic conditions by in vitro gastrointestinal digestion, which could maintain a higher phenolic concentration in the bloodstream and be beneficial for human health. This study could provide a scientific basis for hulless barley DF as valuable food additives.

Enzyme-responsive turn-on nanoprobes for in situ fluorescence imaging and localized photothermal treatment of multidrug-resistant bacterial infections.

Sensitive diagnosis and elimination of multidrug-resistant bacterial infections at an early stage remain paramount challenges. Herein, we present a gelatinase-responsive turn-on nanoprobe for in situ near-infrared (NIR) fluorescence imaging and localized photothermal treatment (PTT) of in vivo methicillin-resistant Staphylococcus aureus (MRSA) infections. The designed nanoprobe (named AuNS-Apt-Cy) is based on gold nanostars functionalized with MRSA-identifiable aptamer and gelatinase-responsive heptapeptide linker (CPLGVRG)-cypate complexes. The AuNS-Apt-Cy nanoprobe is non-fluorescent in aqueous environments due to the fluorescence resonance energy transfer between the gold nanostar core and cypate dye. We demonstrate that the AuNS-Apt-Cy nanoprobe can achieve MRSA targeting and accumulation as well as gelatinase (overexpressed in MRSA environments)-responsive turn-on NIR fluorescence due to the cleavage of the CPLGVRG linker and localized in vitro PTT via a mechanism involving bacterial cell wall and membrane disruption. In vivo experiments show that the AuNS-Apt-Cy nanoprobe can enable rapid (1 h post-administration) and in situ turn-on NIR fluorescence imaging with high sensitivity (105 colony-forming units) in diabetic wound and implanted bone plate mouse models. Remarkably, the AuNS-Apt-Cy nanoprobe can afford efficient localized PTT of diabetic wound and implanted bone plate-associated MRSA infections under the guidance of turn-on NIR fluorescence imaging, showing robust capability for early diagnosis and treatment of in vivo MRSA infections. In addition, the nanoprobe exhibits negligible damage to surrounding healthy tissues during PTT due to its targeted accumulation in the MRSA-infected site, guaranteeing its excellent in vivo biocompatibility and solving the main bottlenecks that hinder the clinical application of PTT-based antibacterial strategies.

Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis.

Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca2+/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca2+/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.

Combinative treatment of ß-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation.

Background and Purpose: RAS mutations limit the effectiveness of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in combination with chemotherapy for metastatic colorectal cancer (mCRC) patients. Therefore, new cell death forms have focused on identifying indirect targets to inhibit Ras-induced oncogenesis. Recently, emerging evidence has shown the potential of triggering ferroptosis for cancer therapy, particularly for eradicating aggressive malignancies that are resistant to traditional therapies. Methods: KRAS mutant CRC cell HCT116 and Lovo were treated with cetuximab and ß-elemene, a bioactive compound isolated from Chinese herb Curcumae Rhizoma. Ferroptosis and epithelial-mesenchymal transformation (EMT) were detected in vitro and in vivo. Orthotopic CRC animal model were established and the tumor growth was monitored by IVIS bioluminescence imaging. Tumor tissues were collected to determine ferroptosis effect and the expression of EMT markers after the treatment. Results: CCK-8 assay showed that synergetic effect was obtained when 125 µg/ml ß-elemene was combined with 25 µg/ml cetuximab in KRAS mutant CRC cells. AV/PI staining suggested a non-apoptotic mode of cell death after the treatment with ß-elemene and cetuximab. In vitro, ß-elemene in combination with cetuximab was shown to induce iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of HO-1 and transferrin, and downregulation of negative regulatory proteins for ferroptosis (GPX4, SLC7A11, FTH1, glutaminase, and SLC40A1) in KRAS mutant CRC cells. Meanwhile, combinative treatment of ß-elemene and cetuximab inhibited cell migration and decreased the expression of mesenchymal markers (Vimentin, N-cadherin, Slug, Snail and MMP-9), but promoted the expression of epithelial marker E-cadherin. Moreover, ferroptosis inhibitors but not other cell death suppressors abrogated the effect of ß-elemene in combination with cetuximab on KRAS mutant CRC cells. In vivo, co-treatment with ß-elemene and cetuximab inhibited KRAS mutant tumor growth and lymph nodes metastases. Conclusions: Our data for the first time suggest that the natural product ß-elemene is a new ferroptosis inducer and combinative treatment of ß-elemene and cetuximab is sensitive to KRAS mutant CRC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for CRC patients with RAS mutations.

Thermal-Disrupting Interface Mitigates Intercellular Cohesion Loss for Accurate Topical Antibacterial Therapy.

Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug-resistant pathogens. Although several strategies such as photothermal therapy and magneto-thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal-disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat-responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy.

Label-free diagnosis for colorectal cancer through coffee ring-assisted surface-enhanced Raman spectroscopy on blood serum.

Surface-enhanced Raman spectroscopy (SERS) is garnering considerable attention for the swift diagnosis of pathogens and abnormal biological status, that is, cancers. In this work, a simple, fast and inexpensive optical sensing platform is developed by the design of SERS sampling and data analysis. The pretreatment of spectral measurement employed gold nanoparticle colloid mixing with the serum from patients with colorectal cancer (CRC). The droplet of particle-serum mixture formed coffee-ring-like region at the rim, providing strong and stable SERS profiles. The obtained spectra from cancer patients and healthy volunteers were analyzed by unsupervised principal component analysis (PCA) and supervised machine learning model, such as support-vector machine (SVM), respectively. The results demonstrate that the SVM model provides the superior performance in the classification of CRC diagnosis compared with PCA. In addition, the values of carcinoembryonic antigen from the blood samples were compiled with the corresponding SERS spectra for SVM calculation, yielding improved prediction results.

Soil C, N, and P distribution as affected by plant communities in the Yellow River Delta, China.

Soil carbon (C), nitrogen (N) and phosphorus (P) are important soil properties linked to nutrient limitation and plant productivity in terrestrial ecosystems. Up to 90% of the Yellow River Delta (YRD), China has been affected by soil salination due to groundwater overdraft, improper irrigation, land use and land cover change. The objective of this study is to evaluate the impact of different plant communities on soil quality in a saline-alkaline system of the YRD. We investigated the vertical distribution and seasonal variation of soil C, N, and P, and C:N ratio by choosing four dominant plant communities, namely, alfalfa grassland (AG), Chinese tamarisk (CT), locust forest (LF) and cotton field (CF). The results showed that the concentrations of soil organic carbon (SOC) and total nitrogen (TN) in CT and LF were always higher than that in AG and CF, especially in the topsoil layer (p<0.05), then gradually decreased with soil depth increasing (p<0.05). The C:N ratio was generally lower, and the average C:N ratio was higher in LF (11.55±1.99) and CT (11.03±0.47) than in CF (10.05±1.25) and AG (9.11±1.11) (p<0.05). The available phosphorus (AP) was highest in CT in Spring, while it was highest in CF in Summer and Autumn. It is worth noting that the soil AP concentrations were always low, particularly in AG (< 6.29 mg kg-1) and LF (< 4.67 mg kg-1), probably linked to P poorly mobile in the saline-alkaline region. In this study, soil nutrients in natural plant communities are superior to farmland, and are significantly affected by the types of plant community; therefore, we suggest that protection of natural vegetation and development of optimal vegetation are critical to restoring land degradation in the YRD.

Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.

Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.

Traditional Chinese medicine on treating chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that traditional Chinese medicine (TCM) can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. In this systematic review, we aim to evaluate the effectiveness and safety of TCM for chronic prostatitis/chronic pelvic pain syndrome. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to May 2019. The quality of the included randomized controlled trials (RCTs) will be evaluated with the risk of bias (ROB) tool and evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation (GRADE). STATA 13.0 and Revman 5.3 will be used to perform a systematic review and meta-analysis to synthesize direct and indirect evidence. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of TCM for treating chronic prostatitis/chronic pelvic pain syndrome. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019131527.

Traditional Chinese medicine on treating epididymitis: A systematic review and meta-analysis protocol.

BACKGROUND: Epididymitis is a common disease in nonspecific infections of the male reproductive system according to the clinical incidence of acute epididymitis and chronic epididymitis. Many clinical trials have proven that Chinese medicine has a significant effect in the treatment of epididymitis. In this systematic review, we aim to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) for epididymitis. METHODS: We will search for PubMed, Cochrane Library, AMED, Embase, WorldSciNet, Nature, Science online, China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of TCM for treating epididymitis. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.Registration number: PROSPERO CRD42019130569.

Traditional Chinese medicine on treating premature ejaculation: A systematic review and meta-analysis.

BACKGROUND: Premature ejaculation is a form of male sexual dysfunction. As people's lifestyle changes and the population ages, the incidence of premature ejaculation continues to increase. Many clinical trials have proven that Chinese medicine has a significant effect in the treatment of premature ejaculation. In this systematic review, we aim to evaluate the effectiveness and safety of Traditional Chinese medicine for premature ejaculation. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of premature ejaculation. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for treating premature ejaculation. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017065316.

Effectiveness comparison of a Chinese dicitraditionalmene formula Wuzi Yanzong Pill and its analogous prescriptions for the treatment of oligoasthenozoospermia: A systematic review and meta-analysis protocol.

BACKGROUND: Among male sterility factors, oligoasthenozoospermia is the most common. As people's lifestyle changes and the population ages, the incidence of oligoasthenozoospermia continues to increase. The studies have shown that about 15% of married couples in the world are affected by infertility, among which infertility caused by male factors alone accounts for about 50%. Many clinical trials have proven that Wuzi Yanzong Pill has a significant effect in the treatment of oligoasthenozoospermia. In this systematic review, we aim to evaluate the effectiveness and safety of Wuzi Yanzong Pill for oligoasthenozoospermia. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online, and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of oligoasthenozoospermia. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Wuzi Yanzong Pill for treating oligoasthenozoospermia. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019119170.

Effectiveness comparisons of acupuncture for chronic prostatitis/chronic pelvic pain syndrome: A Bayesian network meta-analysis protocol.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on CP/CPPS. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by grading of recommendations assessment, development, and evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform a NMA to synthesize direct and indirect evidence. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111408.

A NanoFlare-Based Strategy for In Situ Tumor Margin Demarcation and Neoadjuvant Gene/Photothermal Therapy.

Accurate tumor margin demarcation in situ remains a paramount challenge. Herein, a NanoFlare (also known as spherical-nucleic-acid technology) based strategy is reported for in situ tumor margin delineation by transforming and amplifying the pathophysiological redox signals of tumor microenvironment. The NanoFlare designed (named AuNS-ASON) is based on gold nanostar (AuNS) coated with a dense shell of disulfide bridge-inserted and cyanine dyes-labeled antisense oligonucleotides (ASON) targeting survivin mRNA. The unique anisotropic ASON-spike nanostructure endows the AuNS-ASON with universal cellular internalization of tumor cells, while the disulfide bridge inserted confers response specificity toward redox activation. In vitro experiments demonstrate that the AuNS-ASON can discriminate tumor cells rapidly with activated fluorescence signals (>100-fold) in 2 h, and further achieve synergistic gene/photothermal tumor cells ablation upon near-infrared laser irradiation. Remarkably, in situ tumor margin delineation with high accuracy and outstanding spatial resolution (<100 µm) in mice bearing different tumors is obtained based on the AuNS-ASON, providing intraoperative guidance for tumor resection. Moreover, the AuNS-ASON can enable efficient neoadjuvant gene/photothermal therapy before surgery to reduce tumor extent and increase resectability. The concept of NanoFlare-based microenvironment signal transformation and amplification could be used as a general strategy to guide the design of activatable nanoprobes for cancer theranostics.