Comparison of the efficacy of Hydroquinone cream versus Hydroquinone cream plus Danggui Shaoyao powder in the treatment of melasma.

Introduction: Melasma is an acquired hypermelanosis and occurs in areas exposed to sunlight. Aim: To investigate the effectiveness of Danggui Shaoyao powder (DSP) as a complementary drug in the treatment of melasma. Material and methods: A total of 40 melasma patients over the age of 18 who met the inclusion criteria entered the study randomly in two DSP + Hydroquinone (DSP + H) and Hydroquinone (H) groups. Results: At the beginning of the study, the average MASI score of the two groups of patients had no statistical difference (DSP + H: 15.79 ±1.01 vs. H: 15.37 ±1.17, p = 0.23). But from the eighth week of treatment, the MASI score of the patients decreased significantly and in the DSP + H group it decreased statistically significantly compared to the H group (DSP + H: 5.83 ±0.97 vs. H: 8.29 ±2.23, p < 0.001 for the eighth week and DSP + H: 3.60 ±0.58 vs. H: 5.52 ±1.73, p < 0.001 for the twelfth week of the treatment). It means after 12 weeks of treatment, the average MASI score of patients in the DSP + H group decreased by 77.26 ±2.70%, but in the grroup H, it decreased by 64.31 ±9.68% (p < 0.001). Dynamic PGA showed that excellent treatment occurred in 65% of the + H group H, but only 20% of the H group (p = 0.01). Conclusions: Oral DSP for 12 weeks along with hydroquinone cream can significantly reduce the MASI score of melasma patients and increase the patients' recovery and satisfaction.

Sorafenib and tetrakis (4-carboxyphenyl) porphyrin assembled nanoparticles for synergistic targeted chemotherapy and sonodynamic therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a high degree of malignancy and mortality. Sorafenib (SOR), a multi-kinase inhibitor, is clinically used in the treatment of HCC. However, SOR suffers from serious side effects and drug resistance. The development of novel therapeutic strategies for HCC therapy is urgently needed. Sonodynamic therapy (SDT) has unique advantages in treating deep tumors due to the merits of deep tissue penetration, low side effects, and the absence of drug resistance. Here, we developed multifunctional nanoparticles (NPs) termed SOR-TCPP@PEG-FA by assembling SOR, tetrakis (4-carboxyphenyl) porphyrin (TCPP), and folic acid (FA)-modified DSPE-PEG. The FA group enhances the tumor targeting capability of these NPs, while TCPP generates ROS under ultrasound (US) irradiation, which are toxic to tumor cells, and SOR with chemotherapeutic effects is released, thus realizing the synergistic SDT and chemotherapy of tumors.

Metabolomics study of graphene nuangong acupoint plaster for primary dysmenorrhea.

Primary dysmenorrhea is a common gynecological disease with typical clinical symptoms and diverse treatment methods. Acupoint patch therapy is one of the traditional external treatments of traditional Chinese medicine, with a long history, and has been widely used in the treatment of many diseases in China. Graphene nuangong acupoint plaster (GNGAP) developed based on traditional acupoints and new materials have been used in the clinical treatment of primary dysmenorrhea, and satisfactory therapeutic effects have been achieved. However, the underlying mechanisms of GNGAP still need further investigation. In this study, we used estradiol benzoate combined with oxytocin intraperitoneally to establish dysmenorrhea model rats, and observed the torsion response, uterine organ coefficients, prostaglandin levels and metabolite changes of rats with dysmenorrhea model after the intervention of GNGAP, to elucidate the mechanism of the effect of GNGAP. Compared with normal rats, the dysmenorrhea model rats exhibited increased writhing response and latency time, increased uterine organ coefficient, and significant changes in 79 metabolites. Twenty-three significantly enriched pathways were discovered, including amino acid metabolism, arachidonic acid metabolism, pyrimidine metabolism, and ovarian steroidogenesis, which may be involved in the pathogenesis of primary dysmenorrhea. Compared with the model group, the torsion response, latency time and uterine organ coefficient of rats in the acupoint patch group were significantly improved, and nine uterine metabolites were significantly altered, among which metabolites such as 4-pyridoxic acid, d-glucarate and Phenol were identified as potential biomarkers for the therapeutic effects of GNGAP. Vitamin B6 metabolism, Ascorbate and aldarate metabolism and Tyrosine metabolism were enriched in nine metabolic pathways. These findings contribute to the screening study of potential pathological metabolic pathways in primary dysmenorrhea. Additionally, they reveal the biological effects of GNGAP in the treatment of primary dysmenorrhea at the metabolite level.

[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

In vitro and in vivo Inhibitory Activity of C-glycoside Flavonoid Extracts from Mung Bean Coat on Pancreatic Lipase and α-glucosidase.

Mung bean is a kind of legume commonly eaten by human. In the present study, a HPLC method for analyzing of two C-glycoside flavonoids, isovitexin and vitexin, in Mung bean was developed. Results showed that the flavonoids are mainly existed in Mung bean coat (MBC), while kernel contains very trace. The extraction of C-glycoside flavonoids from MBC was optimized. MBC extracts with isovitexin and vitexin contents of 29.0 ± 0.28% and 35.8 ± 0.19% were obtained with yield of 1.6 ± 0.21%. MBC extracts exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.147 mg/ml and 0.226 mg/ml, respectively. The inhibitory kinetics revealed that MBC extracts showed mixed-type inhibition on these enzymes. Fluorescence quenching titration confirmed the binding of MBC extracts with the enzyme proteins. In vivo study revealed that pre-administration with MBC extracts significantly reduced the triglyceride absorption. Furthermore, it also improved postprandial hyperglycemia in rats through the inhibition of α-glucosidase.

An oral NoV-rAd5 vaccine with built-in dsRNA adjuvant elicits systemic immune responses in mice.

Norovirus (NoV) is an enteric pathogen notorious for causing epidemics of acute gastroenteritis. An effective vaccine against NoV is therefore urgently needed. A short double-stranded RNA (dsRNA) has been described that acts as a retinoic-acid-inducible gene-I agonist to induce the production of type I interferon; it also exhibits adjuvant activity. Using built-in dsRNA of different lengths (DS1 and DS2), we developed a recombinant adenovirus 5 (rAd5) expressing NoV VP1, and evaluated its immunogenicity following oral administration in a mouse model. An in vitro study demonstrated that the dsRNA adjuvants significantly enhanced VP1 protein expression in infected cells. The oral administration of both rAd5-VP1-DS vaccines elicited high serum levels of VP1-specific IgG and blocking antibodies, as well as strong and long-lasting mucosal immunity. There was no apparent difference in immunostimulatory effects in immunised mice between the two dsRNA adjuvants. This study indicates that an oral NoV-rAd5 vaccine with a built-in dsRNA adjuvant may be developed to prevent NoV infection in humans.

Selenium toxicity and bioaccumulation in selenium-enriched fly (Chrysomya megacephala) maggots.

Selenium (Se) is an essential trace element for human health, and as a potential animal feed, the Chrysomya megacephala (Fabricius) fly is rich in protein and fat. By using different concentrations of sodium selenite (0, 30, 50, 70 mg kg-1), the possibility of biological Se enrichment in C. megacephala (Fabricius) maggots (CMMs) was investigated. The accumulation, Se speciation, enzymatic activity, and concentrations of copper (Cu), zinc (Zn), chromium (Cr), and cadmium (Cd) in the maggots were also determined. Transcriptomics was also used to investigate the mechanism of the Se response to CMM genes. The results showed that the CMMs had a survival rate of > 80% at Se exposure concentrations ranging from 0 to 100 mg kg-1. The optimal concentration of sodium selenite for CMM growth was 50 mg kg-1, and the weight, protein content, and total Se accumulation of the larvae (10.8 g, 53.5%, and 72.6 ± 3.36 mg kg-1 (DW), respectively) were considerably higher than the control and other exposure doses (p < 0.05). In addition, Se improved the ability of maggots to absorb Cu and Zn, decreased malondialdehyde (MDA) and lipid peroxidation, but improved the antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, Se negatively affected the absorption of Cd and Cr. According to the transcriptomic findings, Se supplementation can boost protein synthesis and control both antioxidant and non-antioxidant enzyme activity in CMMs. Therefore, our findings showed that Se-enriched CMMs may counteract the toxicity of Cd and Cr, and Se is an effective supplement for improving the consumption safety of cultured animals fed containing CMMs.

Seven diterpenoids from the resin of Pinus yunnanensis Franch and their anti-inflammatory activity.

Phytochemical investigation of the 95% ethanol extract from Pinus yunnanensis Franch resin induced the isolation of six previously unreported diterpenoids pinuyunnanacids K - N, P - Q, a nor-diterpenoid with a novel skeleton pinuyunnanacid O and six known analogues. Their structures were elucidated by spectroscopic analysis and computational methods, including nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, calculated NMR chemical shifts method and electronic circular dichroic (ECD) spectra. All the compounds were analyzed for anti-inflammatory activity through western blotting and cell viability, compounds 2, 10 and 12 significantly downregulated the protein expression of iNOS at the concentration of 40 µM. At the same time, compounds 10 and 12 decreased the expression of COX-2 in LPS-treated RAW264.7 (leukemia cells in mouse macrophage) cells at the concentration of 40 µM.

Proteomic analysis of rat colonic mucosa following acupuncture treatment for irritable bowel syndrome with diarrhea.

To investigate the molecular pathological mechanisms of irritable bowel syndrome with diarrhea (IBS-D) and elucidate the effects of acupuncture on IBS-D colonic mucosa protein abundance in rats, a label-free high-throughput liquid chromatography-tandem mass spectrometry (LC-MS)-based proteomics analysis was used to survey the global changes of colonic mucosa proteins between different groups. Sixteen Sprague-Dawley (SD) male rats were randomly divided into four groups: the control group (C); the IBS-D model group (M); the syndrome differentiation acupuncture group (SD) and the traditional acupuncture group (T). IBS-D model rats were obtained using the CAS (chronic acute combining stress model) method. Comparative bioinformatics analysis of the proteomic data was analyzed using MaxQuant software, Perseus software, online tools DAVID, VENNY and STRING. Functional enrichment and network analyses revealed a close relationship between IBS-D and several biological processes including energy metabolism, muscular excitation/contraction, and both traditional acupuncture and syndrome differentiation acupuncture can reverse the impairments of normal energy metabolism. Moreover, the syndrome differentiation acupuncture can regulate the protein cluster relating inflammation, wound repair and cell protection against oxidative stress which is associated with acupuncture analgesic effect. Differentially expressed proteins Atp5a1 and Bpnt1 were selected as representative proteins and subjected to western blotting. In conclusion, our study provides further insight into the pathological and molecular mechanisms of IBS-D and acupuncture treatments, and serves as an experimental basis for clinical applications.

Vitamin C intake and multiple health outcomes: an umbrella review of systematic reviews and meta-analyses.

The purpose of this article was to assess the existing systematic reviews and meta-analyses for the association between vitamin C intake and multiple health outcomes. A total of 76 meta-analyses (51 papers) of randomised controlled trials and observational studies with 63 unique health outcomes were identified. Dose-response analysis showed that vitamin C intake was associated with reduced risk of all-cause mortality, cardiovascular disease (CVD), oesophageal cancer, gastric cancer, cervical cancer and lung cancer with an increment of 50-100 mg per day. Beneficial associations were also identified for respiratory, neurological, ophthalmologic, musculoskeletal, renal and dental outcomes. Harmful associations were found for breast cancer and kidney stones for vitamin C supplement intake. The benefits of vitamin C intake outweigh the disadvantages for a range of health outcomes. However, the recommendation of vitamin C supplements needs to be cautious. More prospective studies and well-designed randomised controlled trials (RCTs) are needed.

Ranunculus ternatus Thunb extract attenuates renal fibrosis of diabetic nephropathy via inhibiting SMYD2.

CONTEXT: Ranunculus ternatus Thunb (Ranunculaceae), (RTT) is used clinically for the treatment of tuberculosis or as tumour adjuvant therapy, but its potential effect on diabetic nephropathy (DN) has not been studied. OBJECTIVE: To investigate the effect of RTT extract in renal fibrosis of DN. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into four groups (n = 12). Diabetes mellitus (DM) mice were induced by streptozotocin (STZ, 55 mg/kg/day) for five consecutive days and treated by RTT extract (2 g/kg). Afterward, blood glucose, HE and Masson staining were assayed. The expression levels of Vimentin, ɑ-SMA, TNF-ɑ, NF-κB p-p65, NF-κB p65, SMYD2, H3K36me3, H3K4me3 were determined by western blots. Firbronectin was respectively assayed by western blot and immunofluorescent staining. RESULTS: RTT extract significantly ameliorated renal injury and renal fibrosis in the renal tissue of STZ-induced diabetic mice as demonstrated by the decreased expression level of Fibronectin (65%), Vimentin and α-SMA (75% & 53%). In addition, the levels of TNF-α (57%), NF-κB p-p65 and NF-κB p65 (35% & 25%) were elevated in the DN mice. Importantly, these were alleviated after RTT extract treatment. Moreover, we observed that the protein levels of SMYD2 (30%), H3K36me3 and H3K4me3 (53% & 75%) were reduced in DN mice after treatment with RTT extract. DISCUSSION AND CONCLUSIONS: RTT extract mediates antifibrotic effects and anti-inflammatory responses in STZ-induced DN mainly through suppressing SMYD2 activation and H3K36me3 and H3K4me3 protein expression. RTT extract might have therapeutic potential against high glucose-induced nephropathy.

Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by platelet function tests and mean platelet volume.

BACKGROUND: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated. METHODS: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2-3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer. RESULTS: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P <  0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P <  0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701-0.875, P <  0.001) in receiver-operating characteristic curve analysis. CONCLUSIONS: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

[Effect of cotton-moxibustion on chronic eczema and quality of life].

OBJECTIVE: To compare the therapeutic effect between cotton-moxibustion and compound flumetasone ointment, and observe the effect on quality of life in patients with chronic eczema. METHODS: A total of 66 patients with chronic eczema were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, cotton-moxibustion was adopted on target skin lesion, once a day, 3 cones a time. In the control group, external application of compound flumetasone ointment was given twice a day. The treatment for 3 weeks was required in the both groups. Before treatment and 1,2,3 weeks into treatment, scores of visual analogue scale (VAS), eczema area and severity index (EASI) and dermatology life quality index (DLQI) were observed, and the recurrence rate was evaluated in the follow-up one month after treatment. RESULTS: Compared before treatment, the VAS scores of 1,2,3 weeks into treatment, the EASI and DLQI scores of 2,3 weeks into treatment were decreased in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The follow-up recurrence rate in the observation group were lower than the control group (P<0.05). CONCLUSION: Cotton-moxibustion can effectively improve the pruritus symptom, skin lesion and quality of life in the patients with chronic eczema, the therapeutic effect is superior to the external application of compound flumetasone ointment.

Effects of tonifying kidney and strengthen bone therapy on non-dialysis patients with chronic kidney disease-mineral and bone disorder: A protocol for the systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Correction of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) disorders is the standard of treatment in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), but the side effects and adverse reactions brought by western medicine (WM) are still the main problems. More importantly, the lack of protection of kidney function in the treatment greatly affects the health of patients. Although traditional Chinese medicine (TCM), specifically tonifying kidney and strengthen bone (TKSB) therapy is wildly applied for patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we pretent to conduct this protocol to evaluate the efficacy and safety of TKSB therapy combined with WM for non-dialysis patients with CKD-MBD. METHODS: A system research of randomized controlled trials (RCTs) of TKSB therapy for CKD-MBD will be conducted by 2 investigators from 7 electronic databases. Methodological quality evaluations will be performed by using the Cochrane collaboration tool and data analysis will be conducted by RevMan V5.3 software and STATA v15.0. RESULTS: The results of this paper will be submitted to a peer-reviewed journal for publication. CONCLUSION: This research will determine the safety and efficacy of TKSB therapy in treating non-dialysis patients with CKD-MBD. INPLASY REGISTRATION NUMBER: INPLASY2020120086.

Antibacterial Activity of Porous Gold Nanocomposites via NIR Light-Triggered Photothermal and Photodynamic Effects.

Phototherapeutic approaches, including photothermal therapy (PTT) and photodynamic therapy (PDT), have become a promising strategy to combat microbial pathogens and tackle the crisis brought about by antibiotic-resistant strains. Herein, porous gold nanoparticles (AuPNs) were synthesized as photothermal agents and loaded with indocyanine green (ICG), a common photosensitizer for PDT, to fabricate a nanosystem presenting near-infrared (NIR) light-triggered synchronous PTT and PDT effects. The AuPNs can not only convert NIR light into heat with a high photothermal conversion efficiency (50.6-68.5%), but also provide a porous structure to facilely load ICG molecules. The adsorption of ICG onto AuPNs was mainly driven by electrostatic and hydrophobic interactions with the surfactant layer of AuPNs, and the aggregate state of ICG significantly enhanced its generation of reactive oxygen species. Moreover, taking advantage of its synergistic PTT and PDT effect, the hybrid nanocomposites displayed a remarkable antibacterial effect to the gram-positive pathogen Staphylococcus aureus (S. aureus) upon 808 nm laser irradiation.

Effect of cotton-moxibustion on chronic eczema and quality of life / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between cotton-moxibustion and compound flumetasone ointment, and observe the effect on quality of life in patients with chronic eczema.@*METHODS@#A total of 66 patients with chronic eczema were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, cotton-moxibustion was adopted on target skin lesion, once a day, 3 cones a time. In the control group, external application of compound flumetasone ointment was given twice a day. The treatment for 3 weeks was required in the both groups. Before treatment and 1,2,3 weeks into treatment, scores of visual analogue scale (VAS), eczema area and severity index (EASI) and dermatology life quality index (DLQI) were observed, and the recurrence rate was evaluated in the follow-up one month after treatment.@*RESULTS@#Compared before treatment, the VAS scores of 1,2,3 weeks into treatment, the EASI and DLQI scores of 2,3 weeks into treatment were decreased in the both groups (@*CONCLUSION@#Cotton-moxibustion can effectively improve the pruritus symptom, skin lesion and quality of life in the patients with chronic eczema, the therapeutic effect is superior to the external application of compound flumetasone ointment.

Icariin Alleviates Glucocorticoid-Induced Osteoporosis through EphB4/Ephrin-B2 Axis.

PURPOSE: Glucocorticoid (GC) is the most important risk factor for osteoporosis (OP); in the present study, we examined the potential mechanism of icariin, a natural bioactive compound isolated from the traditional Chinese herbal Epimedium, for GC-induced OP to explore its potential therapeutic effect. METHODS: We used a GC-induced OP mice model and treated with icariin. Pathological changes were measured by H&E staining, and the effects of icariin on osteoblasts and osteoclasts were measured by immunohistochemistry (IHC) staining and western blot (WB) analyses, while trabecular bone parameters were detected by micro-CT imaging in vivo. RESULTS: The results showed that in GC-induced OP symptoms, icariin treatment significantly increased the density of the trabecular bone when exposed to GC, revealed by H&E staining and micro-CT imaging. IHC staining showed that GC-induced OP had a lower EphB4 expression and higher Ephrin-B2 expression, but icariin could promote EphB4 while suppressing Ephrin-B2 expression. The WB results also provided evidence of the same protein expression trend, showing that the osteoblast marker OCN and the EphB4 downstream factor RhoA in the GC group were decreased, while both OCN and RhoA expression were significantly increased and the Ephrin-B2 downstream factor Grb4 in in GC group was increased after icariin treatment. CONCLUSION: Icariin could improve the characteristics of OP through regulating the balance of the EphB4/Ephrin-B2 pathway. Further preclinical trial is needed to provide certainty of clinical benefits for OP patients.

Photosensitizer-Modified MnO2 Nanoparticles to Enhance Photodynamic Treatment of Abscesses and Boost Immune Protection for Treated Mice.

The emergence of drug-resistant bacteria and easy recurrence has been challenging in the clinical treatment of skin abscesses resulting from bacterial infections (e.g., by Staphylococcus aureus (S. aureus)). Herein, an antibacterial nanoagent capable of modulating the abscess microenvironment is designed to enhance photodynamic treatment of skin abscesses, and subsequently activate the immune system to effectively prevent abscess recurrence. In the system, manganese dioxide nanoparticles (MnO2 NPs) with high catalytic reactivity toward H2 O2 are modified with photosensitizer chlorine e6 (Ce6) and coated with polyethylene glycol (PEG). The obtained Ce6@MnO2 -PEG NPs, by triggering the decomposition of lesion endogenous H2 O2 , are able to effectively relieve the hypoxic abscess microenvironment during S. aureus infection. The light-triggered photodynamic bacterial killing effect could thus be remarkably enhanced, resulting in effective in vivo therapy of S. aureus-induced skin abscesses. Interestingly, a notable pathogen-specific immunological memory effect against future infection by the same species of bacteria is elicited after such treatment, owing to the release of bacterial antigens post photodynamic therapy (PDT) together with the adjuvant-like function of manganese ions to activate the host immune system. This work thus presents a new type of photodynamic nanoagent particularly promising for highly effective light-triggered abscess treatment and prevention of abscess recurrence.

[Warm acupuncture improves arthritic injury by down-regulating expression of skeleton proteins in rats with knee osteoarthritis].

OBJECTIVE: To investigate the effect of warm acupuncture on chondrocyte cytoskeleton protein Rho associa-ted protein kinase (ROCK)/ monopherine domain kinase 1 (LIMK1)/Cofilin signaling of synovial tissue of the knee-joint in knee osteoarthritis (KOA) rats, so as to explore its mechanisms underlying improvement of KOA. METHODS: One hundred-twenty SD rats (half male and half female) were randomly divided into 5 groups: normal control, model, acupuncture, moxibustion and warm acupuncture, with 24 rats in each group. The KOA model was established by injection of 4% Papain (0.25 mL/kg) into the right knee cavity on day 1, 3 and 7. Rats in the acupuncture, moxibustion and warm acupuncture groups were treated with manual acupuncture, moxibustion and warm acupuncture stimulation of "Neixiyan"(EX-LE4), "Waixiyan"(EX-LE5) and "Zusanli"(ST36), respectively for 20 min, once a day for 21 days. The volume of the right knee-joint was measured by using drainage method and its width measured using a vernier caliper. The histopathological changes of the right knee cartilage were observed after H．E. stain, and scored (0 to 14 points) with reference to Markin's methods. The expression levels of ROCK, Cofilin, phospho-Cofilin, LIMK1 and phospho-LIMK1 proteins of the right knee synovial tissue were detected by Western blot. RESULTS: After modeling, the width and the volume since day 6 of the right knee-joint and Markin score of the cartilage, as well as the expression levels of ROCK, phospho-Cofilin, and phospho-LIMK1 proteins were significantly increased in the model group in contrast to the normal control group (P<0.05，P<0.01). Following the interventions, the width and the volume since day 12 of the right knee-joint and Markin score of the cartilage, as well as the expression levels of ROCK, phospho-Cofilin, and phospho-LIMK1 proteins were reversed in the three treatment groups (P<0.05). The effect of warm acupuncture was significantly superior to that of both simple acupuncture and simple moxibustion in decreasing the width and the volume since day 15 of the right knee-joint and Markin score of the cartilage, as well as in down-regulating the expression levels of ROCK, phospho-Cofilin and phospho-LIMK1 proteins (P<0.05). No significant differences were found between the acupuncture and moxibustion groups in deceasing all the aforementioned indexes (P>0.05)．. CONCLUSION: Acupuncture, moxibustion and warm acupuncture can reduce arthritic injury in KOA rats, which is closely associated with their effects in down-regulating the expression of chondrocyte cytoskeletal proteins ROCK, phospho-Cofilin and phospho-LIMK1. The efficacy of warm acupuncture is evidently superior to that of simple acupuncture and simple moxibustion.

Effects of oligosaccharide-sialic acid (OS) compound on maternal-newborn gut microbiome, glucose metabolism and systematic immunity in pregnancy: protocol for a randomised controlled study.

INTRODUCTION: The gut microbiota participates in multiple human biological processes, including metabolism and immune responses. During pregnancy, the dynamics of gut microbiota is involved in physiological adaptation. The disturbed profile of microbiome is associated with maternal complications, such as gestational diabetes mellitus (GDM), which further transfers to the offspring and influence their metabolic and immunological functions in the long term. Prebiotics targeting the gut microbiota and modulating metabolic and immune functions have been shown to be effective in non-pregnant populations with metabolic syndrome. Hence, we propose the use of a prebiotic supplement, oligosaccharide-sialic acid (OS) from the first trimester until delivery in pregnant women, can benefit maternal/new-born gut microbiome, glucose metabolism and innate immunity. METHODS AND ANALYSIS: In this prospective double-blinded randomised clinical trial, recruited singleton pregnancies will be stratified by body mass index (BMI) and randomly assigned to consume the OS preparation or placebo daily from the first trimester. At seven later time points (before and after recruitment in the first trimester, in the middle and third trimesters, before delivery, at birth and 42 days postpartum), compliance will be evaluated and/or biological samples will be collected. Along with maternal clinical information, questionnaires on lifestyle and infant development will be recorded. The primary outcomes are the effect of OS on the maternal-offspring gut microbiome and GDM incidence. The secondary outcomes are maternal glycolipid biochemical parameters, cytokine profiles, weight gain during pregnancy and infant morbidities, growth and development. The study aims to validate the effects of OS on reducing maternal morbidity within different BMI groups. The multiple dimensional dataset generated from the study includes clinical and lifestyle-related information, various biological markers and associated protective or risk factors for morbidity and prognosis. An extended follow-up through 42 days after birth could further explore the intrauterine influence on the long-term health of offspring. ETHICS AND DISSEMINATION: This protocol has been approved by Peking University First Hospital, National Unit of Clinical Trial Ethics Committee (reference number: 164). The results are expected to be published in scientific manuscripts by 2021. TRIAL REGISTRATION NUMBER: ChiCTR1800017192.