Monitoring Enzymatic Reaction Kinetics and Activity Assays in Confined Nanospace.

Enzyme-mediating biotransformations commonly occur in micro- and nanospace, which is crucial to maintain the essential biochemical processes and physiological functions in living systems. Probing enzyme-catalytic reactions in a biomimetic fashion remains challenging due to the lack of competent tools and methodology. Here, we show that studying enzymatic reaction kinetics can be readily achieved by a well-designed solid-state nanopore. Using tyrosine as a classical substrate, we quantitatively characterize the catalytic activity of tyrosinase (TYR) and tyrosine decarboxylase (TDC) in a nanoconfined space. Tyrosine was first immobilized in the nanopipette, wherein the active sites of tyrosine were left unoccupied. When successively exposed to TYR and TDC, a two-step cascade reaction can spontaneously take place. In this process, the surface wettability and charge of the nanopipette stemming from the catalytic products can sensitively regulate ion transport and ionic current rectification behavior, which were monitored by ionic current signal. In this biomimetic scenario, we obtained the enzymatic reaction kinetics of monophenyl oxidase that were not previously actualized in the conventional macroenvironment. Significantly, TYR showed higher enzyme activity, with a Km value of 1.59 mM, which was lower than that measured in a free and open space (with a Km of 3.01 mM). This suggests that tyrosine should be the most appropriate substrate of TYR, thus improving our understanding of tyrosine-associated biochemical reactions. This work offers an applicable technical platform to mimic enzyme-mediated biotransformations and biometabolisms.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Tuning quantum dots emission on DNA tetrahedron/silica nanosphere/graphene oxide nanointerface for ratiometric fluorescence assay of Pb2+ in multiplex samples.

BACKGROUND: Assembling framework nucleic acid (FNA) nanoarchitectures and tuning luminescent quantum dots (QDs) for fluorescence assays represent a versatile strategy in analytical territory. Rationally, FNA constructs could offer a preferential orientation to efficiently recognize the target and improve detection sensitivity, meanwhile, regulating size-dependent multicolor emissions of QDs in one analytical setting for ratiometric fluorescence assay would greatly simplify operation procedures. Nonetheless, such FNA/QDs-based ratiometric fluorescence nanoprobes remain rarely explored. RESULTS: We designed a sensitive and signal amplification-free fluorescence aptasensor for lead ions (Pb2+) that potentially cause extensive contamination to environment, cosmetic, food and pharmaceuticals. Red and green emission CdTe quantum dots (rQDs and gQDs) were facilely prepared. Moreover, silica nanosphere encapsulating rQDs served as quantitative internal reference and scaffold to anchor a predesigned FNA and DNA sandwich containing Pb2+ binding aptamer and gQD modified DNA signal reporter. On binding of Pb2+, the gQD-DNA signal reporter was set free, resulting in fluorescence quenching at graphene oxide (GO) interface. Owing to the rigid structure of FNA, the fluorescence signal reporter orderly arranged at the silica nanosphere could sensitively respond to Pb2+ stimulation. The dose-dependent fluorescence signal-off mode enabled ratiometric analysis of Pb2+ without cumbersome signal amplification. Linear relationship was established between fluorescence intensity ratio (I555/I720) and Pb2+ concentration from 10 nM to 2 µM, with detection limit of 1.7 nM (0.43 ppb), well addressing the need for Pb2+ routine monitoring. The designed nanoprobe was applied to detection of Pb2+ in soil, cosmetic, milk, drug, and serum samples, with the sensitivity comparable to conventional ICP-MS technique. SIGNIFICANCE: Given the programmable design of FNA and efficient recognition of target, flexible tuning of QDs emission, and signal amplification-free strategy, the present fluorescence nanoprobe could be a technical criterion for other heavy metal ions detection in a straightforward manner.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Universal Sublimation Strategy to Stabilize Single-Metal Sites on Flexible Single-Wall Carbon-Nanotube Films with Strain-Enhanced Activities for Zinc-Air Batteries and Water Splitting.

Single-metal-site catalysts have recently aroused extensive research in electrochemical energy fields such as zinc-air batteries and water splitting, but their preparation is still a huge challenge, especially in flexible catalyst films. Herein, we propose a sublimation strategy in which metal phthalocyanine molecules with defined isolated metal-N4 sites are gasified by sublimation and then deposited on flexible single-wall carbon nanotube (SWCNT) films by means of π-π coupling interactions. Specifically, iron phthalocyanine anchored on the SWCNT film prepared was directly used to boost the cathodic oxygen reduction reaction of the zinc-air battery, showing a high peak power density of 247 mW cm-2. Nickel phthalocyanine and cobalt phthalocyanine were, respectively, stabilized on SWCNT films as the anodic and cathodic electrocatalysts for water splitting, showing a low potential of 1.655 V at 10 mA cm-2. In situ Raman spectra and theoretical studies demonstrate that highly efficient activities originate from strain-induced metal phthalocyanine on SWCNTs. This work provides a universal preparation method for single-metal-site catalysts and innovative insights for electrocatalytic mechanisms.

A comparative study on the clinical and magnetic resonance imaging features between seronegative and seropositive rheumatoid arthritis.

OBJECTIVES: Seronegative rheumatoid arthritis (SNRA) is less common and less known compared with seropositive rheumatoid arthritis (SPRA). The aim of this study was to characterise the clinical and magnetic resonance imaging (MRI) features of SNRA and investigate the associated factors of structural damage. METHODS: We retrospectively collected newly diagnosed RA patients who had MRI data of the hands at baseline. The clinical and MRI features and treatment responses during the 12-month follow-up were compared between SNRA and SPRA. The associated factors of the erosion rate were analysed. RESULTS: A total of 310 RA patients were included in this study. Compared with SPRA, SNRA had a higher level of inflammation (p-values were all <0.001), a higher incidence of low bone mineral density (p=0.009), but a lower erosion score (p<0.001) and a lower probability of interstitial lung disease (ILD) (p=0.019). The main eroded bones were different between SNRA (the scaphoid and the lunate) and SPRA (the capitate and the hamate). In the multivariate analysis, synovitis score, the levels of IL-6 and TNF-α, and hyperglobulinaemia were positively associated with the erosion rate of SNRA (p-values were all <0.05). During the 12-month follow-up, the treatment response between the two groups was comparable (p-values were all >0.05). CONCLUSIONS: SNRA had more severe inflammation but milder erosion compared with SPRA. SNRA with severe inflammation or hyperglobulinaemia needs the same powerful therapy of SPRA to prevent erosion progression.

Catalyst-Oriented Design Based on Elementary Reactions (CODER) for Triarylamine Synthesis.

Recently, the application of computational tools to the rational design of catalysts has received considerable attention, but progress has been limited by the reliance on databases and because mechanistic data have been almost neglected. Herein, we report a new strategy for catalyst design, designated catalyst-oriented design based on elementary reactions (CODER), which fully utilizes mechanistic data, combines the strengths of computational tools and researcher experience. CODER enabled the development of extremely efficient Pd catalysts for C-N coupling, which markedly improved the efficiency of the synthesis of widely used triarylamine optoelectronic materials by enhancing the turnover numbers (up to 340000) to 1-3 orders of magnitude towards literature values.

Framework Nucleic Acid-Based Multifunctional Tumor Theranostic Nanosystem for miRNA Fluorescence Imaging and Chemo/Gene Therapy.

Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a pressing endeavor. Here, we report a multifunctional framework nucleic acid (FNA) nanosystem for simultaneous imaging of microRNA-21 (miR-21) and combined chemo/gene therapy. To achieve this, two FNA nanoarchitectures labeled with Cy5/BHQ2 signal tags were designed, each of which contained an AS1411 aptamer, two pairs of DNA/RNA hybrids, a pH-sensitive DNA catcher, and doxorubicin (DOX) intercalating between cytosine and guanine in the tetrahedral DNA nanostructure (TDN). In the acidic tumor microenvironment, the DNA catchers spontaneously triggered to form an i-motif and create an FNA dimer (dFNA) while releasing DOX molecules to exert a cytotoxic effect. In addition, the overexpressed miR-21 in tumor cells dismantled the DNA/RNA hybrids to produce vascular endothelial growth factor-associated siRNA via a toehold-mediated strand displacement reaction, thus enabling a potent RNA interfering. Also importantly, the liberated miR-21 could initiate cascade-reaction amplification to efficiently activate the Cy5 signal reporters, thereby realizing on-site fluorescence imaging of miR-21 in living cells. The exquisitely designed FNA-based nanosystem showed favorable biocompatibility and stability as well as acid-driven DOX release characteristics. Owing to the aptamer-guided targeting delivery, specific uptake of the FNA-based theranostic nanosystem by HepG2 cells was verified with confocal laser scanning microscopy and flow cytometry analyses, which therefore resulted in apoptosis of HepG2 cells while doing minimal damage to normal H9c2 and HL-7702 cells. Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.

An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.

Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH 5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH 7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.

Highly Regioselective Cobalt-Catalyzed Hydroboration of Internal Alkynes.

Herein, we report the development of new Co complexes that have cyclopropane-based diphosphine ligands and can catalyze highly chemo-, regio-, and stereoselective hydroboration reactions of unsymmetrical internal alkynes. These reactions exhibited unusual regioselectivity: specifically, reactions of aryl alkyl internal alkynes showed excellent cis-ß-addition selectivity, and reactions of dialkyl internal alkynes gave excellent cis-α-addition selectivity. Highly regioselective hydroboration of unsymmetrical dialkyl internal alkynes cannot be achieved by other known methods. The reactions described herein are highly synthetically useful, particularly for the stereoselective synthesis of trisubstituted alkenylborates and alkenes. Mechanistic studies indicate that a CoI -H species is a plausible active catalyst and the rigid structure of the cyclopropane skeleton of the ligands and the crowded reaction pocket were responsible for the unprecedented regioselectivity.

The IL-33/ST2 Axis Promotes Primary Sjögren's Syndrome by Enhancing Salivary Epithelial Cell Activation and Type 1 Immune Response.

The molecular mechanisms of primary Sjögren's syndrome (pSS) are poorly understood. In this study, we explored the role of the IL-33/ST2 axis in the development of pSS. In the mouse model of experimental Sjögren's syndrome, we found that the saliva flow rate at weeks 4 and 30 was preserved in IL-33-/- and ST2-/- mice, compared with that of wild-type mice. At week 30 of experimental Sjögren's syndrome induction, the histological score, anti-nuclear Ab levels, and numbers of Th1 and B cells in draining lymph nodes of the salivary gland were lower in the IL-33-/- and ST2-/- mice, whereas Th17 cells and regulatory T cells were not changed. Primary salivary gland epithelial cells expressed the IL-33 receptor ST2. After stimulation with rIL-33, salivary gland epithelial cells increased the transcriptional levels of CD86 and CCL2, accompanied by the activation of the NF-κB inflammatory pathway. There was a synergistic effect between rIL-33 and rIL-12 in augmenting the production of IFN-γ in CD4+ T cells. In the pSS patients, the expression of IL-33 was elevated in the labial salivary gland, with the number of IL-33+ cells positively correlated with the score of the EULAR (European Alliance of Associations for Rheumatology) Sjögren's syndrome disease activity index (ESSDAI). ST2 was highly expressed in the cytoplasm of ductal epithelial cells, with low levels of expression in lymphatic infiltration sites. Our data suggest that the IL-33/ST2 axis may promote the development of pSS by enhancing salivary epithelial cell activation and the type 1 immune response.

Rational assembly of RGD/MoS2/Doxorubicin nanodrug for targeted drug delivery, GSH-stimulus release and chemo-photothermal synergistic antitumor activity.

Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS2 nanosheets were synthesized and modified by ανß3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS2/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.

Comparative efficacy of different types of acupuncture as adjuvant therapy on carotid atherosclerosis: a protocol for systematic review and network meta-analysis.

INTRODUCTION: Carotid atherosclerosis (CAS) is a disease of the aorta caused by lipid metabolism disorders and local inflammation. Acupuncture combined with traditional western medicine (such as aspirin or atorvastatin) for the treatment of CAS has been widely applied in clinical practice, but there is still a lack of supporting evidence for its efficacy and safety on CAS. Therefore, this systematic review and network meta-analysis (NMA) will summarise the effects of different types of acupuncture treatments on CAS, and a ranking of the therapeutic classes will also be presented, aiming to provide evidence-based medicine for its extensive clinical application. METHODS AND ANALYSIS: Systematic and NMA searches will be conducted in seven electronic databases: PubMed, EMBASE, Medline, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database and Chongqing VIP databases. The search time is from their inception to December 2020, regardless of language and publication type. Randomised controlled trials and controlled clinical trials that include patients with CAS receiving acupuncture therapy compared with a control group will be considered eligible. The primary outcomes include the carotid intima-media thickness and vessel plaque quantification; the secondary outcomes include the carotid plaque Crouse score, greyscale median, lipid levels, the incidence of cardiovascular events, safety and adverse events. The selection of studies, data extraction, quality assessment and risk of bias assessment will be conducted by two independent reviewers. The NMA will be analysed with Stata V.15.0, RevMan V.5.3 software and WinBUGS V.1.4.3. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study as it will be based on de-identified, aggregated published data. We will publish the findings in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020207260.

Structural Lesion Progression of the Sacroiliac Joint and Clinical Features in axSpA During TNFi Reduction: A Retrospective Cohort Study.

Objective: In the clinic, some patients with axial spondyloarthritis (axSpA) have to reduce tumor necrosis factor inhibitor (TNFi) for various reasons. However, there are few studies about how to balance the relapse and TNFi reduction. Here we retrospectively analyzed the structural progression of the sacroiliac joint (SIJ) and clinical features in axSpA during TNFi reduction. Methods: A total of 108 patients with axSpA who followed up for 2 years and completed at least baseline, 12-month, and 24-month MRI scans of SIJ were divided into the tapering group (n = 63) and withdrawal group (n = 45) according to whether TNFi was stopped. We divided 2 years into five intervals, calculating the average dose quotient (DQ) for each of 540 intervals from 108 patients. By using generalized estimation equations with inverse probability of treatment weighting, we investigated the unbiased effects of average DQ on structural progression and treatment response. Results: The disease activity (such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and ASDAS-ESR) and relapse rate were lower in the tapering group at 12 and 24 months (p < 0.05). Δerosion (ß = -0.0100, p = 0.00026) and Δthe Spondyloarthritis Research Consortium of Canada (SPARCC; ß = -0.0959, p < 0.0001) were negatively correlated with average DQ. The average DQ 30 (74.8%, 80.0%) or 41.6 (76.5%, 83%) was best to discriminate the status of treatment response or the status of bone marrow edema, but considering operability, the average DQ 25 (78.0%, 63.3%) was also acceptable especially for patients with HLA-B27 negative and non-severe fat metaplasia. Conclusion: Complete TNFi withdrawal was not recommended. Our study provided a referable strategy (tapering then maintained the average DQ over 30 or even 25) for patients who need TNFi reduction. Higher dose usage of TNFi was associated with a slower erosion progression of SIJ.

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

BACKGROUND: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. OBJECTIVE: To assess the long-term efficacy of acupuncture for CP/CPPS. DESIGN: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). SETTING: Ten tertiary hospitals in China. PARTICIPANTS: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. INTERVENTION: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. RESULTS: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. LIMITATION: Sham acupuncture might have had certain physiologic effects. CONCLUSION: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. PRIMARY FUNDING SOURCE: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report.

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

The efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction: A protocol for systematic review and meta-analysis.

BACKGROUND: Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis. METHODS: All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters' alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion. CONCLUSION: The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction. PROSPERO REGISTRATION NUMBER: CRD42020182990.

Randomized controlled trial for the efficacy of electroacupuncture in the treatment of urge urinary incontinence: A clinical study protocol.

BACKGROUND: Despite that the urge urinary incontinence (UUI) is a nonfatal disease, it can lead to anxiety, embarrassment and depression to the patient. UUI is a common public health problem that can significantly affect the quality of life of the patient. Several conservative treatments have been recommended for the treatment of UUI; however, their efficiency remains unclear, leaving the disease without a real effective treatment. The clinical application of acupuncture to treat UUI is currently considered an effective approach despite the limited evidence that support its efficiency. The aim of this study is to assess the efficacy and safety of electroacupuncture therapy in the treatment of UUI. METHODS AND ANALYSIS: A randomized, parallel, controlled study will be performed. Patients with UUI treated with electroacupuncture group (EA) will compare with the sham-treated sham EA (SA) patients. A total of 100 participants with UUI will be randomly allocated to either the EA or the SA group with a 1:1 ratio. The treatment of UUI patients will performed 3 times per week, for 8 weeks in 30-minute sessions. At the end of the treatment the patients will be followed-up until week 32. The primary outcomes include scores of incontinence questionnaire-short form, the average 24-hour urgency incontinence episodes, and the average 24-hour urge episodes responses from baseline until the 4th, 8th , 24th, and 32nd week. The secondary outcomes included the average 24-hour urine volume and the average 24-hour micturition frequency responses from baseline until the 8th and 32nd week, as well as the change in incontinence quality of life scores from baseline at the 8th and 32nd week. In addition, the degree of satisfaction of the participants undergoing acupuncture treatment will be measured at the 4th and 8th week. The participants' clinical acupuncture expectations were evaluated at baseline, and the questionnaire for urinary incontinence diagnosis was used to identify stress incontinence, mixed urinary incontinence, and urge incontinence at baseline. DISCUSSION: This is a randomized, controlled, observer-blinded trial of electroacupuncture treatment for UUI. The results of this trial will provide more evidence on whether electroacupuncture is efficacious for treating UUI.

Electrostatically mediated layer-by-layer assembly of nitrogen-doped graphene/PDDA/gold nanoparticle composites for electrochemical detection of uric acid.

A layer-by-layer self-assembled nitrogen-doped graphene/PDDA/gold nanoparticle (NDG/PDDA/GNP) composite was described. Citrate-stabilizing gold nanoparticle colloids (GNPs) were electrostatically adsorbed onto NDG nanosheets using a cationic polyelectrolyte, polydiallyldimethylammonium (PDDA), as the linker, thereby creating a high-performance electrochemical interface. The morphology and chemical composition were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, infrared spectroscopy, and Raman spectroscopy. Analytical application was manifested by electrochemical sensing of uric acid (UA), a biomarker involved with a variety of clinical diseases. The prepared nanocomposite exhibited noticeable electroactivity to uric acid oxidation and can give effective peak separation with ascorbic acid and dopamine. Additionally, the nanocomposite practically averted from other potentially interferents including glucose, urea, and serotonin, thus allowing selective voltammetric detection of UA in the biological matrix. Under the optimal condition, peak currents measured by differential pulse voltammetry were proportional to UA concentrations in the range of 0.5~100 µM (R2 = 0.998), with the detection limit of 53 nM. The NDG/PDDA/GNP nanocomposite as presented herein holds potential for aiding the diagnosis of UA-associated diseases and should be a new opportunity for biochemical analysis and biosensing applications. Graphical abstract.