Mediterranean diet for cardiovascular disease: an evidence mapping study.

OBJECTIVE: This study aimed to evaluate the methodological quality of existing meta-analyses (MA) and the quality of evidence for outcome indicators to provide an updated overview of the evidence concerning the therapeutic efficacy of the Mediterranean diet (MD) for various types of CVD. DESIGN: We conducted comprehensive searches of PubMed, Cochrane Library, and Embase databases. The quality of the MA was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence evaluation system was employed to evaluate the quality of evidence for significant outcomes. SETTING: The CVD remains a significant contributor to global mortality. Multiple MA have consistently demonstrated the efficacy of medical interventions in managing CVD. However, due to variations in the scope, quality and outcomes of these reviews, definitive conclusions are yet to be established. PARTICIPANTS: This study included five randomized trials and twelve non-randomized studies, with a combined participant population of 716 318. RESULTS: The AMSTAR 2 checklist revealed that 54·55 % of the studies demonstrated high quality, while 9·09 % exhibited low quality, and 36·36 % were deemed critically low quality. Additionally, there was moderate evidence supporting a positive correlation between MD and CHD/acute myocardial infarction, stroke, heart failure, cardiovascular events, coronary events and major adverse cardiovascular events. CONCLUSIONS: This study indicates that although recognizing the potential efficacy of MD in managing CVD, the quality of the methodology and the evidence for the outcome indicators remain unsatisfactory.

Verapamil modulates NFAT2 to inhibit tumor growth and potentiates PD1ab immune checkpoint inhibitor therapy in cervical cancer treatment.

PURPOSE: Current evidence suggests a high co-prevalence of hypertension and cervical cancer. Accordingly, blood pressure control is indicated during anti-tumor drug therapy in this patient population. Over the past few years, immunotherapy has made great strides in treating different cancers. However, the role and clinical significance of verapamil as a first-line anti-hypertensive drug during immunotherapy remain poorly understood, emphasizing the need for further studies. METHODS: Murine cervical cancer models were employed to assess the effect of verapamil monotherapy and combination with PD1ab. Immunohistochemistry was conducted to quantify the abundance of CD8+ T cell and Ki67+ cells. Several in-vitro and in-vivo assays were used to study the effects of verapamil and explore the preliminary mechanism. RESULTS: Monotherapy with verapamil or PD1ab immune checkpoint inhibitor significantly suppressed the growth of subcutaneously grafted U14 cells in WT BABL/c mice, respectively, with increased survival time of mice. Consistent results were observed in the melanoma model. Furthermore, we substantiated that verapamil significantly impaired tumor proliferation and migration of SiHa human cervical cancer cells in vitro and in vivo. In silico analysis using TCGA data revealed that NFAT2 expression negatively correlated with patient survival. The CCK8 assay revealed that verapamil abrogated the stimulatory effect of NFAT2 after knockdown of NFAT2. CONCLUSIONS: Our results suggest that verapamil inhibits tumor growth by modulating NFAT2 expression and enhancing tumor immune responses to PD1ab, which can be harnessed for cervical cancer therapy, especially for patients with comorbid hypertension. Indeed, further clinical trials are warranted to increase the robustness of our findings.

CRISPR/Cas9-mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host-to-egg immune response.

Schistosomiasis is an important, neglected tropical disease. Schistosoma japonicum can evade host attacks by regulating the host's immunity, causing continuous infection. However, interactions between the host's immune system and S. japonicum are unclear. Our previous research found that the Sj16 protein isolated from S. japonicum has an anti-inflammatory effect in the host. However, the role of Sj16 in the regulation of host immunity in S. japonicum infection is not clear. Here, we applied the CRISPR/Cas9 technique to knockout Sj16 in S. japonicum eggs and investigated the effect of Sj16 in regulating host immunity. We found egg viability decreased after Sj16 knockout. In addition, we found granulomatous inflammation increased, the T-cell immune response enhanced and the immune microenvironment changed in mice model injected with Sj16-knockout eggs by tail vein. These findings suggested that S. japonicum could regulate host immunity through Sj16 to evade the host immune attack and cause continuous infection. In addition, we confirmed the application of CRISPR/Cas9-mediated gene reprogramming for functional genomics in S. japonicum.

Schistosome egg-derived extracellular vesicles deliver Sja-miR-71a inhibits host macrophage and neutrophil extracellular traps via targeting Sema4D.

BACKGROUND: Macrophages and neutrophils are rapidly recruited around Schistosome eggs to form granulomas. Extracellular traps (ETs) of macrophages and neutrophils are part of the pathogen clearance armamentarium of leukocytes. Schistosome eggs possess the ability to resist attack by the host's immune cells and survive by employing various immune evasion mechanisms, including the release of extracellular vesicles (EVs). However, the specific mechanisms by which Schistosome egg-derived EVs (E-EVs) evade the immune response and resist attack from macrophage and neutrophil ETs remain poorly understood. In this study, we aimed to investigate the association between E-EVs and macrophage/neutrophil ETs. METHODS: EVs were isolated from the culture supernatant of S. japonicum eggs and treated macrophages and neutrophils with E-EVs and Sja-miR-71a. The formation of ETs was then observed. Additionally, we infected mice with S. japonicum, administered HBAAV2/9-Sja-miR-71a, and the formation of macrophage ETs (METs) and neutrophil ETs (NETs) in the livers was measured. Sema4D-knockout mice, RNA sequencing, and trans-well assay were used to clarify Sja-miR-71a in E-EVs inhibits METs and NETs formation via the Sema4D/ PPAR-γ/ IL-10 axis. RESULTS: Our findings revealed that E-EVs were internalized by macrophages and neutrophils, leading to the inhibition of METs and NETs formation. The highly expressed Sja-miR-71a in E-EVs targeted Sema4D, resulting in the up-regulation of IL-10 and subsequent inhibition of METs and NETs formation. Sema4D knockout up-regulated IL-10 expression and inhibited the formation of METs and NETs. Furthermore, we further demonstrated that Sja-miR-71a inhibits METs and NETs formation via the Sema4D/ PPAR-γ/ IL-10 axis. CONCLUSIONS: In summary, our findings provide new insights into the immune evasion abilities of Schistosome eggs by demonstrating their ability to inhibit the formation of METs and NETs through the secretion of EVs. This study enhances our understanding of the host-pathogen interaction and may have implications for the development of novel therapeutic approaches. Video Abstract.

Knockout of Sema4D alleviates liver fibrosis by suppressing AOX1 expression.

Liver fibrosis can occur in many chronic liver diseases, and no effective treatments are available due to the poorly characterized molecular pathogenesis. Semaphorin 4D (Sema4D) has immune functions and serves important roles in T cell priming. Here, we found that Sema4D was highly expressed in fibrotic liver, and the expression of Sema4D increased with hepatic stellate cells (HSCs) activation. Knockout of Sema4D alleviated liver fibrosis. Mechanistically, knockout of Sema4D alleviated liver fibrosis by suppressing the expression of AOX1 in retinol metabolism. Further investigation demonstrated that retinoic acid receptor α (RARA), an important nuclear receptor of retinoic acid, was reduced by Sema4D knockout during liver fibrogenesis. Sema4D knockout-mediated suppression of liver fibrosis was partly mediated by regulating the balance of Th1, Th2, Th17, and T-bet+Treg cells via inhibiting AOX1/RARA. Thus, targeting Sema4D may hold promise as a potential therapeutic approach for treating liver fibrosis.

Host liver-derived extracellular vesicles deliver miR-142a-3p induces neutrophil extracellular traps via targeting WASL to block the development of Schistosoma japonicum.

Schistosomiasis is an important neglected tropical disease. Interactions between the host immune system and schistosomes are complex. Neutrophils contribute to clearance of large pathogens primarily by releasing neutrophil extracellular traps (NETs). However, the functional role of NETs in clearing schistosomes remains unclear. Herein, we report that extracellular vesicles (EVs) derived from the liver of Schistosoma japonicum-infected mice (IL-EVs) induce NET release by delivering miR-142a-3p to target WASL and block the development of S. japonicum. WASL knockout accelerated the formation of NETs that blocked further development of S. japonicum. miR-142a-3p and NETs upregulated the expression of CCL2, which recruits macrophages that block S. japonicum development. However, S. japonicum inhibited NET formation in wild-type mice by upregulating host interleukin-10 (IL-10) expression. In contrast, in WASL knockout mice, IL-10 expression was downregulated, and S. japonicum-mediated inhibition of NET formation was significantly reduced. IL-EV-mediated induction of NET formation is thus an anti-schistosome response that can be counteracted by S. japonicum. These findings suggest that IL-EV-mediated induction of NET formation plays a key role in schistosome infection and that WASL is a potential therapeutic target in schistosomiasis and other infectious diseases.

Intra-operative open-lung ventilatory strategy reduces postoperative complications after laparoscopic colorectal cancer resection: A randomised controlled trial.

BACKGROUND: The role of the positive end-expiratory pressure (PEEP) and lung recruitment manoeuvre (LRM) combination (termed open-lung strategy, OLS) during intra-operative mechanical ventilation is not clear. OBJECTIVE: To determine whether an open-lung strategy constituting medium PEEP (6-8 cmH2O) and repeated LRMs protects against postoperative complications in at-risk patients undergoing laparoscopic colorectal cancer resection under low-tidal-volume ventilation. DESIGN: A prospective, assessor-blinded, randomised controlled trial. SETTING: Single university-affiliated hospital, conducted from January 2017 to October 2018. PATIENTS: A total of 280 patients at risk of pulmonary complications, scheduled for laparoscopic colorectal cancer resection under general anaesthesia and low-tidal-volume (6-8 ml kg-1 predicted body weight) ventilation. INTERVENTION: The patients were randomly assigned (1 : 1) to a PEEP of 6-8 cmH2O with LRMs repeated every 30 min (OLS group) or a zero PEEP without LRMs (non-OLS group). MAIN OUTCOME MEASURES: The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring within 7 days after surgery. The secondary outcomes included intra-operative potentially harmful hypotension and the need for vasopressors. RESULTS: A total of 130 patients from each group were included in the primary outcome analysis. Primary outcome events occurred in 24 patients (18.5%) in the OLS group and 43 patients (33.1%) in the non-OLS group [relative risk, 0.46; 95% confidence interval (CI), 0.26 to 0.82; P = 0.009). More patients in the OLS group developed potentially harmful hypotension (OLS vs. non-OLS, 15% vs. 4.3%; P = 0.004) and needed vasopressors (25% vs. 8.6%; P < 0.001). CONCLUSION: Among at-risk patients undergoing laparoscopic colorectal cancer resection under low-tidal-volume ventilation, an open-lung strategy with a PEEP of 6-8 cmH2O and repeated LRMs reduced postoperative complications compared with a strategy using zero PEEP without LRMs. Of note, LRMs should be used with caution in patients with haemodynamic instability. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03160144.

Evaluating the effectiveness of a CRSCE-based de-escalation training program among psychiatric nurses: a study protocol for a cluster randomized controlled trial.

BACKGROUND: The high incidence of workplace violence (WPV) in clinical mental health settings has caused a series of negative impacts on nurses, which has subsequently increased public concern. De-escalation (DE) is recommended as a training program which aims at providing nurses with skills and strategies to more effectively respond and manage WPV. Very few studies have examined the effectiveness of DE training, with current studies possessing various limitations due to their design and small sample sizes. By using a cluster randomized controlled design, the proposed study aims to evaluate the effectiveness of a CRCSE-based DE training programs among psychiatric nurses. METHOD: A cluster randomized controlled trial, with a 6-month follow-up period after the end of the intervention, will be conducted among psychiatric hospitals in Guangdong, China. The randomization unit is each involved psychiatric hospital. Participants in the control group will be assigned to routine WPV management training, participants of the intervention group will undergo the same training while additionally receiving DE training. The DE training will include the following five modules: communication, response, solution, care, and environment (CRSCE). Primary outcomes are objective clinical indicators, which will be extracted from the information systems of the enrolled hospitals. These include the incidence of WPV, injuries caused by WPV, and the use of coercion (physical restraint and seclusion) by nurses. Secondary outcomes, aims at evaluating the effects of DE training on nurses, include the capacity of DE, DE confidence, level of job burnout, and professional quality of life. Data will be collected at baseline (T0), at 3 months (T1, intervention completed), and at 6 months after intervention (T2, follow-up). DISCUSSION: This study will offer trial-based evidence of the efficacy of a DE training program targeted at WPV among psychiatric nurses. DE training is expected to reduce both the total incidence and negative impacts of WPV, with additional improvements in psychiatric nurses' coping skills. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022211 . Prospectively registered on 30 March 2019.

The association between COMT Val158Met polymorphism and migraine risk: A meta-analysis.

Background The COMT Val158Met polymorphism has long been regarded as a risk factor for migraine. The possible association between COMT Val158Met polymorphism and migraine has been evaluated in several studies, but the results are not consistent. Therefore, we conduct this meta-analysis to address these issues. Methods The WEB OF SCIENCE and EMBASE databases were searched for eligible studies. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to estimate the strength of the association between COMT Val158Met polymorphism and migraine. Results Five studies with 979 cases and 1870 controls were ultimately included in the present meta-analysis. The overall data showed no significant association between COMT Val158Met polymorphism and migraine in the multiplicative model (OR = 0.97, 95% CI: 0.78-1.21, p = 0.805) and dominant model (OR = 1.05, 95% CI: 0.75-1.48, p = 0.773), neither in the additive model (OR = 0.97, 95% CI: 0.77-1.23, p = 0.817) nor in the recessive model (OR = 0.88, 95% CI: 0.71-1.09, p = 0.246). In subgroup analysis, both for Caucasian and Asian populations, no statistically significant associations were observed in any genetic models. Conclusions Our meta-analysis suggested that the COMT Val158Met polymorphism was not associated with migraine risk.

Total Oxidant/Antioxidant Status in Sera of Patients with Esophageal Cancer.

BACKGROUND Oxidative stress parameters such as total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) have been studied in breast, thyroid, and simple esophageal cancers (EC). We evaluated these parameters in patients with EC and analyzed their correlations with treatment outcomes. MATERIAL AND METHODS Serum TOS, TAS, and OSI in 92 patients with EC at different clinical stages and in 64 healthy people (controls) were measured. RESULTS Serum TOS, TAS, and OSI were significantly different between patients with EC and healthy controls (all p<0.001); however, there were no significant differences across different clinical stages (all p>0.05). These factors are not correlated with smoking or drinking history (all p>0.05). Patients with EC with higher TOS and OSI and lower TAS had better responses to chemotherapy and/or radiotherapy, but there was no significant correlation with different responses (all p>0.05). In a receiver operating characteristic curve analysis comparing patients with EC with healthy controls, the Youden indices were 0.391, 0.886, and 1, respectively. CONCLUSIONS Serum TOS, TAS, and OSI were significantly different between patients with EC and healthy controls. In patients with EC, these factors were not correlated with smoking or drinking history or with clinical stage. Patients with EC with higher TOS and OSI and lower TAS had a trend towards better outcomes but it did not reach significance. Serum TOS and OSI are potential diagnostic biomarkers that can be used to identify cases of EC.

Dual drug release electrospun core-shell nanofibers with tunable dose in the second phase.

This study reports a new type of drug-loaded core-shell nanofibers capable of providing dual controlled release with tunable dose in the second phase. The core-shell nanofibers were fabricated through a modified coaxial electrospinning using a Teflon-coated concentric spinneret. Poly(vinyl pyrrolidone) and ethyl cellulose were used as the shell and core polymer matrices respectively, and the content of active ingredient acetaminophen (APAP) in the core was programmed. The Teflon-coated concentric spinneret may facilitate the efficacious and stable preparation of core-shell nanofibers through the modified coaxial electrospinning, where the core fluids were electrospinnable and the shell fluid had no electrospinnability. The resultant nanofibers had linear morphologies and clear core-shell structures, as observed by the scanning and transmission electron microscopic images. APAP was amorphously distributed in the shell and core polymer matrices due to the favorite second-order interactions, as indicated by the X-ray diffraction and FTIR spectroscopic tests. The results from the in vitro dissolution tests demonstrated that the core-shell nanofibers were able to furnish the desired dual drug controlled-release profiles with a tunable drug release amount in the second phase. The modified coaxial electrospinning is a useful tool to generate nanostructures with a tailored components and compositions in their different parts, and thus to realize the desired functional performances.

Psychological status of residents at the onset of nationwide COVID-19 lockdown in low- and medium-risk areas of China.

The coronavirus disease 2019 (COVID-19), a dual threat to public physical and mental health, prompted an investigation into the psychological well-being of residents in low- to medium-risk areas of China during the initial stages of the pandemic. We administered WeChat-based questionnaire surveys and employed chi-square tests and multiple logistic regression to analyze correlations between residents' age, gender, education, symptoms, COVID-19 close contact history, information sources, and anxiety, depression, and attitudes toward lockdown measures. We received 10,433 valid questionnaires, revealing 26% anxiety and 19.5% depression. Support for lockdown measures reached 98.2%. Factors such as female gender, self-diagnosed pneumonia symptoms, close contact history, and higher education levels increased anxiety risk. Having a doctorate posed a severe anxiety risk, at 4.5 times (P = .019, 95% CI 1.29-15.73). Older age acted as a protective factor, reducing severe anxiety risk to 0.98 and 0.22 times (P < .001, 95% CI 0.14-0.34). Females with a master degree or below and those receiving COVID-19 information from multiple channels faced higher depression risk. Pneumonia symptoms were a risk for all anxiety and depression degrees. Attitudes toward lockdown measures had no significant impact on psychological status, nor did any of the analyzed factors affect residents' overall attitude toward lockdown. Our findings underscore the need for increased psychological counseling, particularly for young females with lower educational backgrounds or self-suspected infection symptoms, to mitigate mild to moderate anxiety and depression in future epidemics or pandemics. The public, especially those of working age with doctorates or higher education, bears the highest risk of severe anxiety. Lockdown measures enjoy strong support in low- to medium-risk areas of China.

High-intensity focused ultrasound ablation combined with immunotherapy for treating liver metastases: A prospective non-randomized trial.

PURPOSE: Given the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases. METHODS: The study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography. RESULTS: The 14 patients (age range, 35-84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3-21) months. The study is clinically feasible and acceptable to patients. CONCLUSION: This prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

Fast disintegrating quercetin-loaded drug delivery systems fabricated using coaxial electrospinning.

The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS) distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM) images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7) have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP) matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system.

Family Caregivers' Experiences of Caring for Patients With Head and Neck Cancer: A Systematic Review and Metasynthesis of Qualitative Studies.

BACKGROUND: Family caregivers of head and neck cancer (HNC) patients undertook heavy care tasks and role responsibilities. They were facing multiple challenges during the patients' cancer trajectory. OBJECTIVE: The aim of this study was to synthesize existing qualitative evidence regarding family caregivers' experiences of caring for HNC patients. METHODS: A meta-aggregation approach was used. Articles were collected from MEDLINE, EMBASE, CINAHL, Web of Science, PsycINFO, and Cochrane Library. Supplementary resources were collected by scrutinizing reference lists and performing citation tracking. RESULTS: A total of 20 studies were included and synthesized. Three meta-themes covering "accepting the diagnosis and treatment on patients: a distressing process," "facing changes of life and adapting to new roles," and "appreciating the external supports" were identified with 10 subthemes. There was high confidence in the evidence for "facing changes of life and adapting to new roles" and moderate confidence in the evidence for the other 2 meta-themes. CONCLUSIONS: Taking care of HNC patients is a distressing process. Caregivers took on role responsibilities and developed strategies to make adjustments to life changes, so as to provide better care for patients. External supports regarding caregiving and self-care were desired. IMPLICATIONS FOR PRACTICE: Psychological distress was common among caregivers and calls for routine clinical screening. Providing caregivers with practical strategies to deal with daily caregiving tasks was crucial. Healthcare workers can play a critical role in providing tailored support in different caregiving stages. The findings informed the interventions and future research to improve HNC caregivers' experiences.

A bipolar porphyrin molecule for stable dual-ion symmetric batteries with high potential.

The small molecule 5,15-di(thiophen-2-yl) porphyrin (TP) was developed for new dual-ion symmetric organic batteries (DSOBs). It delivered a capacity of 150 mA h g-1 at 0.2 A g-1 with a high voltage of 2.7 V, and up to 1500 cycles were achieved. This work offers a new approach for developing high-performance dual-ion organic symmetric batteries.

Extracellular vesicles derived from Trichinella Spiralis larvae promote the polarization of macrophages to M2b type and inhibit the activation of fibroblasts.

Trichinella spiralis (T. spiralis) is a globally distributed food-borne parasite that can coexist with the host for a long time after infection. Trichinella-derived secretions can regulate the immune response and fibroblasts of the host, but the specific mechanisms involved are still unclear. The purpose of this study was to investigate the role of T. spiralis larvae-derived extracellular vesicles (EVs) and their key miRNAs in the process of T. spiralis-host interaction. In this study, we found that the EVs of T. spiralis larvae, as well as miR-1-3p and let-7-5p, expressed in T. spiralis larvae-derived EVs, can promote the polarization of bone marrow macrophages to M2b type while inhibiting the activation of fibroblasts. These findings will contribute to further understanding of the molecular mechanisms underlying T. spiralis-host interactions.

Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: There has been a rapid increase in the worldwide prevalence of Alzheimer's disease (AD). Previous studies have shown that acupuncture can improve neurological and cognitive function; however, the utility of applying acupuncture in patients with AD remains unclear. This study protocol describes a clinical trial for evaluating the efficacy and safety of acupuncture based on syndrome differentiation with donepezil hydrochloride on cognitive function in patients with AD. METHODS/DESIGN: This multicenter randomized controlled trial commenced on February 1, 2019, at the Shanghai Longhua Hospital of TCM, Shanghai Huashan Hospital of Fudan University, and Shanghai Mental Health Center, and will conclude on June 30, 2022. The study will recruit 184 patients randomly divided into an acupuncture group or a control group at a 1:1 ratio. All participants will receive donepezil hydrochloride (5 mg/day), and those in the acupuncture group will receive acupuncture based on syndrome differentiation with donepezil for 12 weeks. The primary outcome will be the post-treatment change in the Alzheimer's Disease Assessment Scale-cognition score at 12 weeks. The secondary outcomes will be the efficacy scores of the Minimum Mental State Examination, Alzheimer's Disease Cooperative Research Activity-Daily Life, and Quality of Life-Alzheimer's Disease. All assessments will be performed at baseline, after treatment (week 12), and at follow-up (weeks 24 and 36). DISCUSSION: This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of AD. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03810794 . Registered on 17 January 2019.

An engineered probiotic secreting Sj16 ameliorates colitis via Ruminococcaceae/butyrate/retinoic acid axis.

Most inflammatory bowel disease (IBD) patients are unable to maintain a lifelong remission. Developing a novel therapeutic strategy is urgently needed. In this study, we adopt a new strategy to attenuate colitis using the Escherichia coli Nissle 1917 probiotic strain to express a schistosome immunoregulatory protein (Sj16) in the gastrointestinal tract. The genetically engineered Nissle 1917 (EcN-Sj16) highly expressed Sj16 in the gastrointestinal tracts of dextran sulfate sodium-induced colitis mice and significantly attenuated the clinical activity of colitis mice. Mechanistically, EcN-Sj16 increased the intestinal microbiota diversity and selectively promoted the growth of Ruminococcaceae and therefore enhanced the butyrate production. Butyrate induced the expression of retinoic acid, which further attenuated the clinical activity of colitis mice by increasing Treg cells and decreasing Th17. Strikingly, retinoic acid inhibitor inhibited the therapeutic effects of EcN-Sj16 in colitis mice. These findings suggest that EcN-Sj16 represents a novel engineered probiotic that may be used to treat IBD.