Nanoparticles integrated with mild photothermal therapy and oxaliplatin for tumor chemotherapy and immunotherapy.

Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.

Is percutaneous tibial nerve stimulation (PTNS) effective for fecal incontinence (FI) in adults compared with sham electrical stimulation? A meta-analysis.

BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.

A life-course approach to tackling noncommunicable diseases in women.

Women's health has been critically underserved by a failure to look beyond women's sexual and reproductive systems to adequately consider their broader health needs. In almost every country in the world, noncommunicable diseases are the leading causes of death for women. Among these, cardiovascular disease (including heart disease and stroke) and cancer are the major causes of mortality. Risks for these conditions exist at each stage of women's lives, but recognition of the unique needs of women for the prevention and management of noncommunicable diseases is relatively recent and still emerging. Once they are diagnosed, treatments for these diseases are often costly and noncurative. Therefore, we call for a strategic, innovative life-course approach to identifying disease triggers and instigating cost-effective measures to minimize exposure in a timely manner. Prohibitive barriers to implementing this holistic approach to women's health exist in both the social arena and the medical arena. Recognizing these impediments and implementing practical approaches to surmounting them is a rational approach to advancing health equity for women, with ultimate benefits for society as a whole.

[Effects of Organic Fertilizer of Kitchen Waste on Soil Microbial Activity and Function].

Changes in soil microbial activity and ecological function can be used to assess the level of soil fertility and the stability of ecosystems. To assess the fertility and safety of organic fertilizer of kitchen waste (OFK), soils containing 0% (CK), 1%, 3%, and 5% OFK were cultured, and the physical, chemical, and microbial properties of the soils were measured dynamically with routine agrochemical analysis measures and amplicon sequencing. The results showed that compared with those in CK, the contents of organic matter, available phosphorus, available potassium, NH4+-N, and NO3--N in soils with OFK increased by 23.80%-35.13%, 13.29%-29.72%, 16.91%-39.37%, 164.7%-340.2%, and 28.56%-32.71%, respectively. The activities of hydrolases related to the cycle of carbon, nitrogen, and phosphorus (α-glucosidase, leucine aminopeptidase, acid phosphatase, etc.) were also significantly higher than those of the CK treatment. OFK stimulated the growth of soil microorganisms and increased the carbon content of the microbial biomass. The amplicon sequencing analysis found that the microbial community structures of different treatments were significantly different at both the class and genus levels. In addition, it was found that the abundance of beneficial microbes in the soils with OFK increased, whereas pathogenic microbes decreased. RDA results confirmed that soil properties (including soil pH, organic matter, available nutrients, and microbial biomass) had a significant impact on microbial community structure. The results of investing bacterial community based on PICRUSt and FAPROTAX revealed that the function of the soil bacterial community was similar in the four treatments, but OFK supply significantly improved the microbial carbon utilization and metabolic ability. Moreover, by using the FUNGuild software, we found that the application of OFK increased the proportion of saprotroph-symbiotroph and symbiotroph and stimulated the growth of ectomycorrhizal fungi-undefined saprophytic fungi but inhibited plant and animal pathogenic fungi in soil. These results implied that OFK could promote the establishment of symbiotic relationships and inhibit the growth of pathogenic fungi. In summary, OFK could improve soil fertility and hydrolase activity, stimulate the growth of beneficial microorganisms, and defend against pathogens, indicating a promising use as safe and efficient organic fertilizer.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Least Absolute Shrinkage and Selection Operator-Based Prediction of the Binding Constant of p-Sulfonatocalix[6]/[8]arenes with Alkaloids.

p-Sulfonatocalix[n]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA (n = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration. LASSO regression was adopted to investigate the mechanism of the complex of SCnA with alkaloids. The binding constant of alkaloids-SC6A and alkaloids-SC8A was related to the alkaloid alkalinity. Also, the electronegativity, polarization, first ionization potential, hydrogen bond potential, the molecular size, and shape of alkaloids are critical properties to determine alkaloids-SC6A binding constant as well as electronegativity, polarization, hydrophobicity, and the molecular size and shape of alkaloids play an important role for the alkaloids-SC8A binding constant.

Effect of electroacupuncture on inflammatory response and immune cells in mice with chronic inflammatory pain. / ç”µé’ˆå¯¹æ ¢æ€§ç‚Žæ€§ç—›å°é¼ ç‚Žæ€§ååº”å’Œå ç–«ç»†èƒžçš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture(EA) on local inflammatory mediators and macrophage polarization, and immune cells in the spleen of mice with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the hind paw, so as to investigate the immunoinflammatory regulatory mechanisms of EA in relieving pain and swelling in mice with chronic inflammatory pain. METHODS: Thirty C57BL/6 mice were randomly divided into control, model, and EA groups, with 10 mice in each group. Chronic inflammatory pain model were established by subcutaneous injection of 20 µL CFA solution in the left hind paw for 7 consecutive days. After modeling, mice in the EA group received EA at bilateral "Zusanli"(ST36) for 20 min (2 Hz/100 Hz, 1 mA) once a day for 18 consecutive days. Mechanical pain threshold, heat pain thresholds, and paw thickness were measured before and after mode-ling, and after interventions. Western blot was used to detect the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and NOD-like receptor protein 3 (NLRP3) in the paw tissue. Immunohistochemistry was used to detect the positive expression of M1-type macrophage marker inducible nitric oride synthase (iNOS) and M2-type marker CD206 in the paw, and flow cytometry was used to detect the proportion of F4/80+ CD11b+ macrophages, Ly6G+ CD11b+ neutrophils, and CD25+ Foxp3+ regulatory T cells (Treg) in the spleen. RESULTS: Compared with the control group, mechanical pain and heat pain thresholds were significantly reduced(P<0.000 1), while paw thickness, expressions of IL-1ß, TNF-α, and NLRP3 in the paw, and positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly increased (P<0.000 1, P<0.001) in the model group. Compared with the model group, mechanical pain threshold and heat pain thresholds, CD206 positive expression in the paw, and Treg cell proportion in spleen were significantly increased (P<0.01), while paw thickness, the expressions of IL-1ß, TNF-α and NLRP3 in the paw, as well as the positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly reduced (P<0.001, P<0.01, P<0.05)in mice of the EA group after intervention. CONCLUSIONS: EA may alleviate pain and swelling in mice with chronic inflammatory pain by regulating the numbers of macrophages, neutrophils, and Treg cells, as well as promoting M2 polarization of local macrophages and inhibiting the release of pro-inflammatory cytokines.

[Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells].

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

[Application and Development of a Chinese Medicine Meridian and Acupoint Intervention in Nursing Practice].

Chinese medicine advocates a holistic and comprehensive approach that emphasizes differential diagnosis, treatment, and nursing as well as a diverse range of healthcare options. Within Chinese medicine, acupuncture techniques targeting meridians and acupoints are recognized as a suitable healthcare modality for promoting health, preventing diseases, and managing existing conditions. This article was designed to explore the practical application and advancement of acupuncture related to meridians and acupoints in the field of nursing. After introducing the development and current landscape of Chinese medicine healthcare, the application of acupoint stimulation within the context of Chinese medicinal nursing is discussed, taking into account clinical expertise, patient preferences, and safety concerns. Next, empirical findings on the impact of acupoint stimulation interventions are presented in hopes of translating clinical knowledge into evidence-based practice. Lastly, future prospects and investments in Chinese medicinal nursing are outlined. Within the realm of professional nursing practice, attaining proficiency in meridian and acupoint interventions requires comprehensive expertise and skills. Healthcare professionals in the nursing field should contemplate enhancing their knowledge and competencies in Chinese medicinal nursing. By providing the best evidence-based care, possessing specialized expertise, and taking patient preferences into account, the quality and completeness of evidence-based healthcare may be improved.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease.

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

Synergistic impact of co-exposures to whole blood metals on chronic kidney disease in general US adults: a cross­sectional study of the National Health and Nutrition Examination Survey 2011-2020.

The impact of exposure to metals on chronic kidney disease (CKD) has only been investigated in two-way or single metal interactions in previous studies. We investigated the associations between five single metals in blood and their mixed exposure and CKD by using the machine learning approach. Relevant data were extracted from the National Health and Nutrition Examination Survey (NHANES 2011-2020), and the level of five metals in blood detected by inductively coupled plasma mass spectrometry was considered as exposures, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se). The correlations between individual metal and metal mixtures and CKD were then evaluated by survey-multivariable logistic regression (SMLR), generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Altogether, our study included 12,412 participants representing 572.6 million non-institutionalized US adults. Several single metals with the high quartile of exposure showed a positive association with the CKD ratio including Cd [(AOR = 1.873, 95% CI: 1.537, 2.284), Q4], Pb [(AOR = 1.559, 95% CI: 1.295, 1.880), Q4], and total Hg [(AOR = 1.169, 95% CI: 1.018, 1.343), Q2], while Mn [(AOR = 0.796, 95% CI: 0.684, 0.927), Q2] and Se [(AOR = 0.805, 95% CI: 0.664, 0.976), Q4] were negatively associated with the CKD ratio. In light of the positive fit of the WQS regression model, a significantly positive correlation was found between mixed metals and CKD (AOR = 1.373, 95% CI: 1.224, 1.539) after full covariate adjustment, and a similar finding was also detected in the BKMR model. Our study revealed that each single metal including Cd, Pb, and total Hg might have a positive association with CKD while this association was negative for both Mn and Se. The five metals might have a positive joint effect on CKD.

In Situ Rapid Analysis of Squalene, Tocopherols, and Sterols in Walnut Oils Based on Supercritical Fluid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.

Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.

Joint effect of whole blood metals exposure with dyslipidemia in representative US adults in NHANES 2011-2020.

With little knowledge on the joint effects of metal exposure on dyslipidemia, we aimed to investigate the relationship between exposure to metal and dyslipidemia among US adults based on the National Health and Nutrition Examination Survey (NHANES). Based on the five NHANES waves (2011-2020), we selected five metals in blood as exposure, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se), which were detected by inductively coupled plasma mass spectrometry. Survey-multivariable logistic regression, generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR) were performed to determine whether dyslipidemia was associated with single metals or mixed metals. Our study included 12,526 participants aged from 20 to 80, representing 577.1 million non-institutionalized US adults. We found a positive association between several metals including Pb [adjusted odds ratio (AOR) = 1.332, 95%CI: 1.165, 1.522], total Hg (AOR = 1.264, 95%CI: 1.120, 1.427), Mn (AOR = 1.181, 95%CI: 1.046, 1.334), and Se (AOR = 1.771, 95%CI: 1.576, 1.992) and dyslipidemia. According to the WQS approach, metal mixtures were positively associated with dyslipidemia (AOR: 1.310, 95%CI: 1.216, 1.411) after a full-model adjustment. As is shown in the BKMR model, mixed metals tended to be positively associated with dyslipidemia ratios in a significant manner. Females, non-Hispanic White populations, people aged over 60, and those who did a little physical activity had a greater risk for dyslipidemia. Our findings suggest metals including Cd, Pb, Hg, Mn, and Se and their combinations may adversely affect dyslipidemia among US adults. Due to the cross-sectional nature of the study, it is possible that reverse causation may exist.

Endofungal Bacterial Microbiota Promotes the Absorption of Chelated Inorganic Phosphorus by Host Pine through the Ectomycorrhizal System.

Ectomycorrhizal fungi play an irreplaceable role in phosphorus cycling. However, ectomycorrhizal fungi have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. Endofungal bacteria in ectomycorrhizal fruiting bodies are always closely related to the ecological function of ectomycorrhizal fungi. In this study, we explore endofungal bacteria in the fruiting body of Tylopilus neofelleus and their function during the absorption of chelated inorganic phosphorus by host pine through the ectomycorrhizal system. The results showed that the endofungal bacterial microbiota in the fruiting body of T. neofelleus might be related to the dissolution of chelated inorganic phosphorus in soil. The soluble phosphorus content in the combined system of T. neofelleus and endofungal bacteria Bacillus sp. strain B5 was five times higher than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment in the dissolution experiment of chelated inorganic phosphorus. The results showed that T. neofelleus not only promoted the proliferation of Bacillus sp. strain B5 in the combined system but also improved the expression of genes related to organic acid metabolism, as assesed by transcriptomic analysis. Lactic acid content was five times higher in the combined system than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment. Two essential genes related to lactate metabolism of Bacillus sp. strain B5, gapA and pckA, were significantly upregulated. Finally, in a pot experiment, we verified that T. neofelleus and Bacillus sp. strain B5 could synergistically promote the absorption of chelated inorganic phosphorus by Pinus sylvestris in a ternary symbiotic system. IMPORTANCE Ectomycorrhizal fungi (ECMF) have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. In the natural environment, the extraradical hyphae of ECMF alone may not satisfy the phosphorus demand of the plant ectomycorrhizal system. In this study, our results innovatively show that the ectomycorrhizal system might be a ternary symbiont in which ectomycorrhizal fungi might recruit endofungal bacteria that could synergistically promote the mineralization of chelated inorganic phosphorus, which ultimately promotes plant phosphorus absorption by the ectomycorrhizal system.

The effect of externally applied traditional Chinese medicine in diabetic foot: A systematic review and meta-analysis of 34 RCTs.

AIM: This study aimed to investigate the clinical efficacy of externally applied Traditional Chinese Medicine (TCM) on diabetic foot. METHODS: We searched the China Knowledge Network (CNKI), Wanfang Database, PubMed and Web of Science from inception to July 31, 2022, to find all randomized control trials (RCTs) related to externally applied TCMs in diabetic foot treatment. Information about the total effective rate, healing rate, and healing time were extracted. In addition, the relative risk (RR)/odds ratio (OR) or standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated. RESULTS: Finally, a total of 34 RCTs including 3758 patients were included in this meta-analysis. There were 5 articles that reported hydropathic compress with astrogalin, 14 articles that reported MEBO burn cream, 9 articles that reported compound cortex phellodendri liquid and 6 articles that reported Shengji Yuhong ointment. Compared with the basic treatment, the externally applied TCM (astrogalin, MEBO burn cream, compound cortex phellodendri liquid and Shengji Yuhong ointment) combined with basic treatment improved the total effective rate (RR = 1.31 [1.20, 1.42], P < 0.0001) and healing rate (RR = 1.84 [1.56, 2.17], P < 0.0001) and shortened the healing time (SMD = - 2.51 [- 3.39, - 1.63], P < 0.0001). CONCLUSION: Our systematic review and meta-analysis revealed that common TCM applied externally could significantly improve the clinical efficacy comparing to the basic treatment.

Mitochondria-targeted fluorophores for in vivo NIR-II imaging-guided PDT/PTT.

A simple yet powerful D-A type-based NIR-II fluorophore (MTF) with mitochondria targeting was constructed. This mitochondrial targeting dye MTF exhibited not only a photothermal effect but also photodynamic performance, and was further fabricated with DSPE-mPEG to generate nanodots for in vivo experiments, achieving strong NIR-II fluorescence tracing of tumors and impressive NIR-II image-guided photodynamic therapy (PDT) and photothermal therapy (PTT).

Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.

OBJECTIVES: Antimicrobial resistance is a major global threat. Because of the stagnant antibiotic pipeline, synergistic antibiotic combination therapy has been proposed to treat rapidly emerging multidrug-resistant (MDR) pathogens. We investigated antimicrobial synergy of polymyxin/rifampicin combination against MDR Acinetobacter baumannii. METHODS: In vitro static time-kill studies were performed over 48 h at an initial inoculum of ∼107 CFU/mL against three polymyxin-susceptible but MDR A. baumannii isolates. Membrane integrity was examined at 1 and 4 h post-treatment to elucidate the mechanism of synergy. Finally, a semi-mechanistic PK/PD model was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by mono- and combination therapies. RESULTS: Polymyxin B and rifampicin alone produced initial killing against MDR A. baumannii but were associated with extensive regrowth. Notably, the combination showed synergistic killing across all three A. baumannii isolates with bacterial loads below the limit of quantification for up to 48 h. Membrane integrity assays confirmed the role of polymyxin-driven outer membrane remodelling in the observed synergy. Subsequently, the mechanism of synergy was incorporated into a PK/PD model to describe the enhanced uptake of rifampicin due to polymyxin-induced membrane permeabilisation. Simulations with clinically utilised dosing regimens confirmed the therapeutic potential of this combination, particularly in the prevention of bacterial regrowth. Finally, results from a neutropenic mouse thigh infection model confirmed the in vivo synergistic killing of the combination against A. baumannii AB5075. CONCLUSION: Our results showed that polymyxin B combined with rifampicin is a promising option to treat bloodstream and tissue infection caused by MDR A. baumannii and warrants clinical evaluations.

Vitamin C and vitamin D3 alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis.

Background: Previous studies have demonstrated that both vitamin C (VC) and vitamin D3 (VD3) have therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acids via the gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects. Methods: In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VD3 on MAFLD by using a high-fat diet (HFD)-induced obese mouse model. Results: Treatment of mice with VC and VD3 efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD3 showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD3 reshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice. Conclusion: Together, the results indicate that the anti-MAFLD activities of VC and VD3 are linked to improved gut-liver interactions via regulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.

Translating and Validating the Vietnamese Version of the Health Sciences Evidence-Based Practice Questionnaire.

No validated instrument is available for assessing the evidence-based practice capacity of Vietnamese health professionals. This study aimed to translate and validate the Health Sciences Evidence-Based Practice questionnaire (HS-EBP) from English to Vietnamese and ascertain its psychometric properties. Data were collected from two obstetric hospitals in Vietnam. Participants: A total of 343 midwives were randomly selected. The HS-EBP questionnaire was translated by a group of bilingual experts into Vietnamese (HS-EBP-V). Content validity was assessed by two experts. Internal consistency and test-retest reliabilities were assessed using Cronbach's α and intraclass correlation (ICC), respectively. Construct validity was assessed using the contrasted groups approach. As a result, the content validity index of the HS-EBP-V reached 1.0. For the individual subscales, Cronbach's α was 0.92-0.97 and ICC was between 0.45 and 0.66. The validity of the contrasted-groups approach showed discrimination by a significant difference in the subscale scores among diploma holders compared with bachelor's degree holders (p < 0.001). The validation of the HS-EBP questionnaire indicated satisfactory psychometric properties. The results indicate that the HS-EBP is a reliable and valid instrument which assesses the competencies of as well as facilitators of and barriers to the five steps of EBP among midwives. The HS-EBP-V was deemed a reliable and validated tool for assessing the competency and application of EBP among Vietnamese healthcare professionals.

Antifungal alkaloids from Mahonia fortunei against pathogens of postharvest fruit.

Postharvest pathogens can affect a wide range of fresh fruit and vegetables, including grapes, resulting in significant profit loss. Isoquinoline alkaloids of Mahonia fortunei, a Chinese herbal medicine, have been used to treat infectious microbes, which might be effective against postharvest pathogens. The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids, of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum. The antifungal alkaloids could change the mycelium morphology, the total lipid content, and leak the cell contents of B. cinerea. Furthermore, the two most potent antifungal alkaloids, berberine (13) completely inhibited effect on gray mold of table grape at 512 mg L-1, while jatrorrhizine (18) exhibited an inhibition rate > 90% on grape rot at the same concentration, with lower cytotoxicity and residue than chlorothalonil, which suggested that ingredients of M. fortunei might be a low-toxicity, low-residue, eco-friendly botanical fungicide against postharvest pathogens.