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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Effectiveness of CRSCE-Based De-escalation Training on Reducing Physical Restraint in Psychiatric Hospitals: A Cluster Randomized Controlled Trial.

Background: The use of physical restraint (PR) causes clinical and ethical issues; great efforts are being made to reduce the use of PR in psychiatric hospitals globally. Aim: This study aimed to examine the effectiveness of CRSCE-based de-escalation training on reducing PR in psychiatric hospitals. Method: The proposed study adopted cluster randomized controlled trial design. Twelve wards of a psychiatric hospital were randomly allocated to experimental group (n = 6) and control group (n = 6). Wards of control group were assigned to routine training regarding PR; wards of experimental group underwent the same routine training while additionally received CRSCE-based de-escalation training. Before and after CRSCE-based de-escalation training, the frequency of and the duration of PR, and the numbers and level of unexpected events caused by PR, were recorded. Results: After CRSCE-based de-escalation training, the frequency (inpatients and patients admitted within 24 h) of and the duration of PR of experimental group, showed a descending trend and were significantly lower than those of control group (P < 0.01); compared to control group, the numbers of unexpected events (level II and level III) and injury caused by PR of experimental group had been markedly reduced (P < 0.05). Conclusions: CRSCE-based de-escalation training would be useful to reduce the use of PR and the unexpected event caused by PR in psychiatric hospitals. The modules of CRSCE-based de-escalation training can be adopted for future intervention minimizing clinical use of PR. Clinical Trial Registration: This study was registered at Chinese Clinical Trial Registry (Registration Number: ChiCTR1900022211).

Functional Characteristics and Application of Mesenchymal Stem Cells in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a rare, heterogeneous autoimmune and autoinflammatory disease that affects both sexes and all races, although this disease exhibits its highest incidence/prevalence among the black population and shows a predilection for women of reproductive age. Although SLE has no cure, treatment can help decrease its signs and symptoms. Thus, we should focus primarily on personalized treatment. Mesenchymal stem/stromal cells (MSCs), which are multipotent cells capable of differentiating into osteoblasts, chondrocytes, adipocytes, and myoblasts, among other cell types, are potential candidates for use in a promising strategy to treat severe and refractory SLE. MSCs have an immunomodulatory function that can suppress the proliferation and activities of many immune cells, such as T lymphocytes, B lymphocytes, natural killer cells, macrophages and dendritic cells. Substantial progress has recently been made in MSC therapy, and experimental and clinical data suggest that such a therapy is a promising strategy for the treatment of severe and refractory SLE. In this review, we highlight the effects of MSCs on different immune cell types, describe the mechanisms underlying MSC-mediated immunoregulation, and discuss the treatment of SLE with MSCs from different sources in various animal models and clinical applications.

Abnormal thymic B cell activation and impaired T cell differentiation in pristane-induced lupus mice.

Changes in the thymus and potential mechanisms underlying the pathogenesis in pristane-induced lupus (PIL) mice are poorly understood. This study aimed to systematically and specifically examine changes in the thymus and the potential mechanisms responsible for immunological abnormalities in PIL mice. The results showed that PIL mice exhibit serious thymic hyperplasia, an elevated thymus index, a damaged histopathological structure and increased thymocyte apoptosis. We found that thymic T cell differentiation was impaired as the CD4+ CD8+ double-positive (DP) thymocyte frequency significantly decreased, becoming almost absent at 28 weeks after induction, while CD4 CD8- double-negative (DN) thymocytes and CD4+ CD8- single-positive (CD4+ SP) and CD4 CD8+ single-positive (CD8+ SP) cells were increased. This phenomenon might be explained by an inhibition of the DN-to-DP-cell transition and stimulation of DP cell conversion into CD4+ /CD8+ SP thymocytes. Moreover, we discovered a dramatic and abnormal increase in thymic B cells, that was associated with CD19, Irf8, Ebf1, Pax5, Irf4, Blk, CXCL13, CXCR5, CD79a, CD79b, Lyn, Syk, Btk, and BLNK gene accumulation, which exhibited positive interactions. We further verified that the mRNA expression of these genes was significantly upregulated and consistent with the RNA-seq results. These results suggest a role of these genes in the increase of B cells in the thymus of PIL mice. In summary, our results showed the changes in the thymus in PIL and elucidated the immunologic abnormalities of increased B cells, potentially providing insight into the associated molecular mechanisms and facilitating further research.

Earlier Acupuncture Enhancing Long-Term Effects on Motor Dysfunction in Acute Ischemic Stroke: Retrospective Cohort Study.

Stroke is the leading fatal disease in China. This retrospective study aimed to explore the optimal acupuncture intervention time for long-term efficacy on motor dysfunction in patients suffering from acute ischemic stroke through 1-year of follow-up. Three hundred and nine patients collected at Longhua Hospital from January 2016 to December 2017 were classified into 3 groups based on the acupuncture intervention time, including groups A (within 2 days), B (within 3-7 days) and C (within 8-14 days). All patients had received standard treatment combined with acupuncture therapy. Specifically, acupuncture was performed at the acupoints including LI4 (Hegu), ST40 (Fenglong), DU20 (Baihui), and motor area of the scalp, followed by 2 electroacupuncture protocols based on different muscle tensions once a day for 5 days consecutively. The time-effect relationship was assessed using both the Fugl-Meyer Assessment (FMA) and the modified Barthel index (MBI) on the 90th day and 1st year, respectively. Meanwhile, the modified Rankin scale (mRS), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen (FIB) were also measured during the 1-year follow-up. The favorable outcome rate was 74.4%. One-way univariate analysis of variance (ANOVA) revealed significant differences in FMA and MBI on the 90th day among the 3 groups ([Formula: see text] < 0.05), while no significant differences were observed in FMA, MBI or mRS at the 1st year between groups A and B. The levels of hs-CRP and FIB ([Formula: see text] < 0.05) were markedly reduced. Binary logistic regression analysis suggested that patients with atrial fibrillation (AF) (odds ratio (OR): 3.156), chronic kidney disease (CKD) (OR: 2.563), diabetes mellitus (DM) (OR: 2.174) or stroke history (OR: 1.883) were more inclined to recover poorly from nerve function deficit ([Formula: see text] < 0.05). Earlier acupuncture intervention may have a better long-term effect on motor dysfunction and inflammation during the 1-year follow-up. Moreover, acupuncture within 2 days is probably the optimal treatment time for early recovery on the 90th day.

Overview of Meta-Analyses of Five Non-pharmacological Interventions for Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory deficits, cognitive decline, and spatial disorientation. Non-pharmacological interventions to treat AD have been reported in many meta-analyses (MAs), but robust conclusions have not been made because of variations in the scope, quality, and findings of these reviews. Objective: This work aimed to review existing MAs to provide an overview of existing evidence on the effects of five non-pharmacological interventions in AD patients on three outcomes: Mini-Mental State Examination (MMSE), activities of daily living (ADL), and Alzheimer's Disease Assessment Scale-cognitive section (ADAS-cog). Methods: The databases PubMed, Cochrane Library, Embase, and Web of Science were searched to collect MAs of non-pharmacological interventions for AD. Two reviewers independently conducted literature screening, data extraction, and quality assessment. We assessed the quality of MAs with the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 and assessed the evidence quality for significant outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: We found 10 eligible MAs, which included between three (133 patients) and 15 randomized trials (1,217 patients), and five non-pharmacological interventions, namely, acupuncture therapy (40%), exercise intervention (30%), music therapy (10%), cognitive intervention (10%), and repetitive transcranial magnetic stimulation (rTMS) (10%). All the included MAs were critically low to low quality by AMSTAR 2. Acupuncture therapy and exercise intervention showed the preliminary potential to improve ADL and MMSE. rTMS and acupuncture therapy show benefits in decreasing ADAS-cog, and there were some evidence of improved MMSE with cognitive intervention. All these outcomes scored very low quality to moderate quality of evidence on the GRADE system. Conclusions: Non-pharmacological therapy shows promise for the treatment of AD, but there is still a lack of high-quality evidence. In the future, the quality of the original research needs to be improved, and strictly designed MAs should be carried out following methodological requirements.

Sja-miR-71a in Schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D.

Schistosomiasis is characterized by liver fibrosis, and studies have indicated that Schistosoma japonicum (S. japonicum) eggs can limit the progression of liver fibrosis. However, the detailed molecular mechanisms are yet unclear. Extracellular vesicles (EVs) contain a selection of miRNAs for long-distance exchange of information and act as an important pathway for host-parasite communication. This study aimed to explore the potential role of S. japonicum egg-derived EVs and its key miRNA in liver fibrosis. Herein, we found that S. japonicum egg-derived EVs can inhibit the activation of hepatic stellate cells, which is mediated via the high expression of Sja-miR-71a. Sja-miR-71a in EVs attenuates the pathological progression and liver fibrosis in S. japonicum infection. Sja-miR-71a inhibiting TGF-ß1/SMAD and interleukin (IL)-13/STAT6 pathways via directly targeting semaphorin 4D (Sema4D). In addition, Sja-miR-71a can also suppress liver fibrosis by regulating Th1/Th2/Th17 and Treg balance. This study contributes to further understanding of the molecular mechanisms underlying Schistosoma-host interactions, and Sema4D may be a potential target for schistosomiasis liver fibrosis treatment.