Does nature-based social prescription improve mental health outcomes? A systematic review and meta-analysis.

Background: A nature-based social prescription (NBSP) is an approach to improving mental health outcomes that involves prescribing nature-based interventions as complementary or alternative therapy to traditional ones. A variety of advantages are available from NBSP for people looking to enhance their mental well-being. The effect size of the nature-based social prescriptions (NBSPs) has not been thoroughly evaluated by systematic reviews and meta-analyses. Objectives: The current study aimed to analyze existing studies and conduct a meta-analysis to determine the overall effect size of the nature-based social prescriptions (NBSP's) outcomes on mental health. Methods: By choosing the relevant papers from among those that were available, a meta-analysis was carried out in the current study. A systematic search of electronic databases (Pub Med, Web of Science, Scopus, Cochrane Library, Embase, CINAHL, and PsychINFO) was conducted to identify relevant studies. Studies were included if they evaluated the effects of NBSP on mental health outcomes. Effect sizes were calculated using the random effects model. Results: Meta-analysis of interventions statistics shows that CBT (SMD -0.0035; 95% CI: [-0.5090; 0.5020]; Tau^2: 0.1011; Tau: 0.318), digital intervention (SMD -0.3654; 95% CI: [-0.5258; 1.2566]; Tau^2: 0.2976, Tau: 0.5455), music intervention (SMD -2.1281; 95% CI: [-0.4659; 4.7221]; Tau^2: 3.4046; Tau:1.8452), and psychological interventions (SMD -0.8529; 95% CI: [0.3051; 1.4007]; Tau^2: 0.1224; Tau: 0.3499) do not significantly impact. The other interventions [social belongingness, communication training, blue intervention, nature-based education, cognitive behavior group therapy (CBGT), social prescribing coordinator, self-help intervention, participatory, organizational intervention, inpatient services, brief diet, internet-based intervention, prenatal intervention, yoga and meditation, ergonomics training program, yoga nidra intervention, and storytelling] highlighted above are significant. Conclusion: The conclusion of the meta-analysis supports the idea that incorporating nature-based social prescription interventions into mental healthcare plans can effectively complement traditional therapies and improve mental health outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023412458, CRD42023412458.

Traditional Chinese medicine Qingre Huoxue decoction enhances wound healing in through modulation of angiogenic and inflammatory pathways.

This study investigates the therapeutic potential of Qingre Huoxue Decoction (QHD), a traditional Chinese herbal formulation, in promoting wound healing in an imiquimod-induced murine model of psoriasis. The research was driven by the need for effective wound healing strategies in psoriatic conditions, where conventional treatments often fall short. Employing a combination of in vivo and in vitro methodologies, we assessed the effects of QHD on key factors associated with wound healing. Our results showed that QHD treatment significantly reduced the expression of angiogenic proteins HIF-1α, FLT-1, and VEGF, and mitigated inflammatory responses, as evidenced by the decreased levels of pro-inflammatory cytokines and increased expression of IL-10. Furthermore, QHD enhanced the expression of genes essential for wound repair. In vitro assays with HUVECs corroborated the anti-angiogenic effects of QHD. Conclusively, the study highlights QHD's efficacy in enhancing wound healing in psoriatic conditions by modulating angiogenic and inflammatory pathways, presenting a novel therapeutic avenue in psoriasis wound management.

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Daily stress, and mental health of professional degree graduate students in Chinese traditional medicine universities: the mediating role of learning career adaptation.

BACKGROUND: With the expansion of professional degree graduate students' enrollment in China education, the mental health of these professional degree graduate students in medical-related majors who are under pressure of study, scientific research, clinical practice, and employment should not be ignored. What is the mental health level of these graduate students under the effect of learning career adaptation (internal resources) in the face of daily stress (external factors)? The purpose of this study is to discuss the relationship between these variables, and the mediating role of learning career adaptation of professional degree graduate students in traditional Chinese medicine colleges, and universities, to provide a theoretical basis for improving the learning career adaptation of students, and improving the level of mental health. METHODS: A cross-sectional survey was conducted among 1593 professional degree graduate students majoring in clinical medicine, traditional Chinese medicine, and nursing in five traditional Chinese medicine universities. Finally, 660 questionnaires were returned, with a recovery rate of 41.43%. The scores of daily stress, learning career adaptation, and mental health were measured by Daily Stressors Scale for graduate students, graduate-students learning career adaptation scale, and General Mental Health Questionnaire (GHQ-20). Descriptive statistics were used to analyze the status quo of daily stress, learning career adaptation, and mental health. Pearson correlation analysis were used to analyze the relationship between them. we undertake analyses using structural equation modeling to construct the latent variable path model of daily stress, learning career adaptation on mental health. The significance level of the mediating effect was tested by the non-parametric percentile bootstrap method. RESULTS: The scores of mental health, daily stress, and learning career adaptation were 50.56 ± 10.80, 35.12 ± 19.55, and 67.13 ± 7.48 respectively. Daily stress was negatively correlated with the three dimensions of learning career adaptation: career confidence, focus on his career, and career control (P < 0.01). Daily stress was positively correlated with depression and anxiety (P < 0.01). Self-affirmation, depression, and anxiety were negatively correlated with career confidence, focus on his career, and career control (P < 0.05). Learning career adaptation plays a partial mediating role between daily stress, and mental health (p < 0.001), with an intermediate effect value of 0.127, representing 28.54% of the total effect. CONCLUSIONS: Mental health, learning career adaption of medical-related professional degree graduate students in traditional Chinese medical universities were at a moderate degree, and an upper-middle level respectively, while daily stress is to a lesser extent. Learning career adaptation mediates the relationship between daily stress, and mental health partially. To some extent, it can buffer the impact of daily stress on mental health, especially anxiety. The educational administrator could take various measures to improve the mental health of professional degree graduate students. It can also enhance their learning career adaptation from the perspective of individuals, and organizations to improve their mental health.

Long-read sequencing reveals the landscape of aberrant alternative splicing and novel therapeutic target in colorectal cancer.

BACKGROUND: Alternative splicing complexity plays a vital role in carcinogenesis and cancer progression. Improved understanding of novel splicing events and the underlying regulatory mechanisms may contribute new insights into developing new therapeutic strategies for colorectal cancer (CRC). METHODS: Here, we combined long-read sequencing technology with short-read RNA-seq methods to investigate the transcriptome complexity in CRC. By using experiment assays, we explored the function of newly identified splicing isoform TIMP1 Δ4-5. Moreover, a CRISPR/dCasRx-based strategy to induce the TIMP1 exon 4-5 exclusion was introduced to inhibit neoplasm growth. RESULTS: A total of 90,703 transcripts were identified, of which > 62% were novel compared with current transcriptome annotations. These novel transcripts were more likely to be sample specific, expressed at relatively lower levels with more exons, and oncogenes displayed a characteristic to generate more transcripts in CRC. Clinical outcome data analysis showed that 1472 differentially expressed alternative splicing events (DEAS) were tightly associated with CRC patients' prognosis, and many novel isoforms were likely to be important determinants for patient survival. Among these, newly identified splicing isoform TIMP1 Δ4-5 was significantly downregulated in CRC. Further in vitro and in vivo assays demonstrated that ectopic expression of TIMP1 Δ4-5 significantly suppresses tumor cell growth and metastasis. Serine/arginine-rich splicing factor 1 (SRSF1) acts as a onco-splicing regulator through sustaining the inclusion of TIMP1 exon 4-5. Furthermore, CRISPR/dCasRx-based strategies designed to induce TIMP1 exon 4-5 exclusion have the potential to restrain the CRC growth. CONCLUSIONS: This data provides a rich resource for deeper studies of gastrointestinal malignancies. Newly identified splicing isoform TIMP1 Δ4-5 plays an important role in mediating CRC progression and may be a potential therapy target in CRC.

Protection Effect of Elbow Joint Airbag on Patients with Upper Limb Fractures: A Quasi-Randomized Controlled Trial.

Objective: Wound healing is delayed because of swelling after upper limb fracture, and the traditional rehabilitation device used in physical therapy cannot flexibly adjust the fixation. This study aims to evaluate the effect of the designed elbow joint airbag protection device used in patients with upper arm fractures. Methods: This is a quasi-randomized controlled trial. From November 2022 to March 2023, 70 hospitalized patients with unilateral upper arm fractures were recruited from a general tertiary hospital in eastern China. The patients were divided into an experimental group and a control group according to the random number table at 1:1. Among them, 35 patients who received elbow joint airbag protection for post-traumatic limb swelling were assigned to the experimental group, and the other 35 patients were assigned to the control group. The degree of swelling regression, a score of resting pain, and patient comfort level was compared between the two groups. Results: The waiting time from swelling to allowing for surgery and pain score at rest were significantly lower in the experimental group than in the control group (P < .05 and P < .001 respectively). The comfort score of the experimental group was higher than that of the control group (P < .05), and these differences were statistically significant. Conclusions: The elbow joint airbag protection can significantly reduce the waiting time for surgery, lessen the degree of swelling regression, reduce the pain in patients' hands caused by swelling, and significantly improve the comfort level. Hence, it is worth promoting in the clinical practice of orthopedic nursing.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice.

Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor model in both Balb/c nude mice (xenograft), C57BL/6J mice (allograft), and hematogenous metastatic neoplasm in nude mice. NR (400 mg/kg bw) was supplied daily in gavage. In-situ tumor growth or noninvasive bioluminescence were measured to evaluate the effect of NR on the HCC process. HepG2 cells were treated with transforming growth factor-ß (TGF-ß) in the absence/presence of NR in vitro. We found that NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice in both subcutaneous xenograft and hematogenous metastasis models. NR supplementation decreased metastasis to the bone and liver in the hematogenous metastasis model. NR supplementation also significantly decreased the size of allografted tumors and extended the survival time in C57BL/6J mice. In vitro experiments showed that NR intervention inhibited the migration and invasion of HepG2 cells triggered by TGF-ß. In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of HCC progression.

The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials.

OBJECTIVE: Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial. MATERIALS AND METHODS: We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality. RESULTS: Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p < 0.001), estradiol (p < 0.001), progesterone (p < 0.001), luteinizing hormone (p < 0.001), uterine fibroids volume (p < 0.001), uterine volume (p < 0.001), menstrual flow (p < 0.001) and increased clinical efficiency rate (p < 0.001). Meanwhile, GZFL combined with low-dose MFP did not significantly increase the incidence of adverse drug reactions compared with low-dose MFP alone (p = 0.16). The quality of the evidence for the outcomes ranged from "very low" to "moderate." CONCLUSION: This study suggests that GZFL combined with low-dose MFP is more effective and safe in the treatment of UFs, and it is a potential treatment for UFs. However, due to the poor quality of the included RCTs formulations, we recommend a rigorous, high-quality, large-sample trial to confirm our findings.

Influencing factors of self-regulated learning of medical-related students in a traditional Chinese medical university: a cross-sectional study.

BACKGROUND: In recent years, self-regulated learning (SRL) has become a hot topic in medical education. However, the factors that affect the SRL ability of medical-related specialties, such as clinical medicine, traditional Chinese medicine (TCM), and nursing specialty in TCM colleges and universities are unclear. Whether the teaching of learning strategies can help improve students' SRL also needs to be further examined. METHOD: A cross-sectional survey was distributed, and 878 medical-related students who were from a TCM university were recruited for this study. Descriptive statistics illustrated the status quo of SRL and learning strategies, and an independent t-test and analysis of variance were used to analyze the factors associated with SRL. The relationship between SRL and learning strategies was analyzed with multi-linear regression analysis. RESULTS: The scores of SRL on learning motivation, learning setting, self-regulation, and total scores were 34.76 ± 4.62, 41.14 ± 4.30, 39.26 ± 4.74, and 115.16 ± 12.42, respectively. The metacognitive, emotion, cognitive, resource management and total scores of learning strategies were 58.54 ± 12.02, 43.24 ± 8.42, 35.49 ± 7.34, 22.89 ± 4.20, 160.16 ± 29.45, and the mean was all above the midpoint. Learning strategies were positively correlated with SRL (r = 0.421, P < 0.01). Some factors can predict 32% of the variation of SRL, including whether they liked their specialty, educational system, specialty, score ranking, scholarship, whether they were taught by a tutor in middle school, gender, monthly family income, the father's educational background, metacognitive strategy, resource management strategy, and cognitive strategy. CONCLUSIONS: The SRL of medical-related students was better. Learning strategies, as well as personal or social factors, can affect SRL. Educators should pay more attention to the cultivation of learning strategies, exercising learning skills, and monitoring, adjustment, and guidance of learning time. It should adopt various methods to improve the SRL of medical-related students according to the different factors.

Shegan Mahuang Decoction May Reduce Airway Inflammation in Neutrophilic Asthmatic Mice by Improving the Mitochondrial Function of Bronchoalveolar Lavage Fluid Exosomes.

Asthma is a common pulmonary disease mainly caused by the infiltration of neutrophils. There is a limit to the therapeutic effects of the available asthma drugs on neutrophilic asthma. Shegan Mahuang Decoction (SMD) is one of the representative traditional Chinese medicine (TCM) prescriptions for asthma, and it can effectively relieve the clinical symptoms of patients. However, the effect of SMD on the treatment of neutrophilic asthma remains unknown. In this study, a mouse model of neutrophilic asthma induced by lipopolysaccharide (LPS)/ovalbumin (OVA) was established, and the effect of a modified SMD prescription on the model was evaluated. After treatment, SMD was demonstrated to be therapeutically effective on asthmatic mice via airway resistance detection and lung pathology and was able to affect cytokine levels in vivo. Further experiments verified that SMD regulated the expression of mitochondrial function proteins in bronchoalveolar lavage fluid (BALF) exosomes. The results demonstrate that SMD confers a therapeutic effect on a neutrophilic asthma mouse model, and it may reduce neutrophil airway inflammation by regulating myeloid-derived regulatory cell (MDRC) function and airway exosome mitochondrial function.

Epimedium brevicornum Maxim. Extract exhibits pigmentation by melanin biosynthesis and melanosome biogenesis/transfer.

Epimedium brevicornum Maxim. (Epimedii Folium) is a traditional medicine widely utilized in China for sexual dysfunction and osteoporosis treatment. Recently, studies have reported that Epimedium flavonoid icariin displayed hair growth and melanogenic ability by targeting tyrosinase activity. Nevertheless, icariin hydrolysate icariside II and icaritin cause depigmentation due to their tyrosinase inhibition. These pigment functional discrepancies from Epimedium constituents arouse our great interest. Then, this study focused on the pigmentation effects of Epimedii Folium extract (EFE) on melanin synthesis and melanosome biogenesis/transfer, and further identified the bioactive constituents. First, in in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and amount of time in multi-melanocytes, normal human skin tissue, and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented models of N-phenylthiourea-induced zebrafish and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contribute to melanin biosynthesis by activating the MAPK/ERK1/2 signal pathway. In addition, EFE effectively increased melanosome number, accelerated melanosome maturity and cytoplasmic transport through the growth/extension of melanocyte dendrites, and induced melanosome transfer from melanocyte to keratinocyte for pigmentation. The six main flavonoid ingredients were identified among EFE. Compared to others, epimedin B (EB) was confirmed as a high-content, low-toxicity, and effective melanogenic compound in EFE. Taking all these together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornum Maxim., and clarifies its related molecular mechanisms and melanogenesis basis. These results give additional insight into Epimedium herb pharmacology and may provide a novel therapy basis for hypopigmentation disorders.

Swelling of Multilayered Calcium Alginate Microspheres for Drug-Loaded Dressing Induced Rapid Lidocaine Release for Better Pain Control.

The development of effective drug-loaded dressings has been considered a hot research topic for biomedical therapeutics, including the use of botanical compounds. For wound healing, adequate dressings can provide a good microenvironment for drug release, such as lidocaine. Biological macromolecular materials such as alginate show excellent properties in wound management. This study involves the preparation and evaluation of biocompatible multilayered-structure microspheres composed of chitosan, porous gelatin, and calcium alginate microspheres. The multilayered structure microspheres were named chitosan@ porous gelatin@ calcium alginate microspheres (CPAMs) and the drugs were rapidly released by the volume expansion of the calcium alginate microspheres. The in vitro release curve revealed that the peak release of lidocaine from CPAMs was reached within 18[Formula: see text]min. After 21[Formula: see text]min, the remaining lidocaine was then slowly released, and the active drug release was converted to a passive drug release phase. The initial release effect of lidocaine was much better than that reported in the published studies. Additionally, blood coagulation experiments showed that CPAMs coagulated blood in 60[Formula: see text]s, and the blood liquidity of the CPAMs group was worse than that of the woundplast group. Therefore, the coagulation characteristics of CPAMs were superior to the commonly used woundplast containing lidocaine healing gel. These study outcomes indicated that the CPAMs acted as fast-release dressings for faster pain control and better coagulation properties.

Influence of ripening stage and meteorological parameters on the accumulation pattern of polyphenols in greengages (Prunus mume Sieb. Et Zucc) by widely targeted metabolomic.

Greengage is a Chinese traditional medicine food homology plant that contains abundant polyphenols. Greengages with different levels of maturity have different medicinal functions and applications. Therefore, this study comprehensively analysed the phenolic compounds in greengage of whole mature stage. Notably, the influence of climate conditions on greengage polyphenol synthesis was deeply explored. The polyphenols of greengages were profiled based on the widely targeted metabolomic technology using ultra-performance liquid chromatography-electrospray ionisation triple quadrupole mass spectrometry (UPLC-QTRAP-MS/MS). A total of 214 polyphenols were detected, covering 11 subclasses. During the ripening of greengages, these polyphenols first increased and then decreased, peaking during the swell stage. Multivariate statistical methods, including redundancy analysis (RDA), random forest analysis, Mantel test, and Spearman's correlation indicated that temperature, sunshine hours, humidity, and radiation were important factors driving the formation and changes in the polyphenols of greengages. In particular, flavanones and flavonols, showed a structure-dependent response to temperature and radiation.

Salvia-Nelumbinis naturalis improves lipid metabolism of NAFLD by regulating the SIRT1/AMPK signaling pathway.

BACKGROUND: Salvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway. METHODS: Male C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and ß-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism. RESULTS: Dynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation. CONCLUSIONS: Taken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/ß-catenin pathway.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover， western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.

Efficacy and safety of Qinxiang Qingjie oral solution for the treatment of influenza in children: a randomized, double-blind, multicenter clinical trial.

Background: Qinxiang Qingjie (QXQJ), an oral solution containing various Chinese herbs, is indicated for pediatric upper respiratory tract infections. The treatment of influenza also shows potential advantages in shortening the duration of illness and improving symptoms. However, there is still a lack of high-quality clinical evidence to support this. The trial was to explore the efficacy and safety of QXQJ for treating pediatric influenza and provide an evidence-based basis for expanding its applicability. Methods: A randomized, double-blind, double-dummy, positive-controlled, multicenter clinical trial was conducted in 14 hospitals in China. Children aged 1-13 years with influenza and "exterior and interior heat syndromes" as defined by traditional Chinese medicine (TCM) were randomly assigned to two groups with 1:1 radio. Children in the test group received QXQJ oral solution and oseltamivir simulant, while the control group received oseltamivir phosphate granules and QXQJ simulant. The duration of treatment was five days, followed by a two-day follow-up period. The primary endpoint was the clinical recovery time. Secondary endpoints included the time to defervescence, incidences of complications and severe or critical influenza, negative conversion rate, improvement of TCM syndromes, and safety profiles of the therapeutics, which mainly contained the adverse clinical events and adverse drug reactions. Results: A total of 231 children were randomized to either the QXQJ (n=117) or oseltamivir (n=114) group. The FAS and PPS results showed that both groups experienced a median clinical recovery time of three days (P>0.05). The median time to defervescence of both groups were 36 hours in FAS and PPS (P>0.05), and two groups did not differ in terms of the other secondary endpoints (P>0.05). 14 patients (12.39%) in the QXQJ group and 14 patients (12.50%) in the oseltamivir group reported at least one adverse event, respectively. One serious adverse event occurred in the QXQJ group. There was no significant difference in the incidence of adverse events or adverse drug reactions between the groups. Conclusions: The efficacy of QXQJ oral solution was comparable to that of oseltamivir for treating influenza in children, with an acceptable safety profile. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021060.

Scoparone Improves Nonalcoholic Steatohepatitis Through Alleviating JNK/Sab Signaling Pathway-Mediated Mitochondrial Dysfunction.

The activated c-Jun N-terminal kinase (JNK) specifically combined with SH3 domain-binding protein 5 (Sab) may mediate damage to the mitochondrial respiratory chain. Whether mitochondrial dysfunction induced by the JNK/Sab signaling pathway plays a pivotal role in the lipotoxic injury of nonalcoholic steatohepatitis (NASH) remains a lack of evidence. Scoparone, a natural compound from Traditional Chinese Medicine herbs, has the potential for liver protection and lipid metabolism regulation. However, the effect of scoparone on NASH induced by a high-fat diet (HFD) as well as its underlying mechanism remains to be elucidated. The HepG2 and Huh7 cells with/without Sab-knockdown induced by palmitic acid (PA) were used to determine the role of JNK/Sab signaling in mitochondrial dysfunction and cellular lipotoxic injury. To observe the effect of scoparone on the lipotoxic injured hepatocytes, different dose of scoparone together with PA was mixed into the culture medium of HepG2 and AML12 cells to incubate for 24 h. In addition, male C57BL/6J mice were fed with an HFD for 22 weeks to induce the NASH model and were treated with scoparone for another 8 weeks to investigate its effect on NASH. Molecules related to JNK/Sab signaling, mitochondrial function, and lipotoxic injury were detected in in vitro and/or in vivo experiments. The results showed that PA-induced activation of JNK/Sab signaling was blocked by Sab knockdown in hepatocytes, which improved mitochondrial damage, oxidative stress, hepatosteatosis, cell viability, and apoptosis. Scoparone demonstrated a similar effect on the PA-induced hepatocytes as Sab knockdown. For the NASH mice, treatment with scoparone also downregulated the activation of JNK/Sab signaling, improved histopathological changes of liver tissues including mitochondrial number and morphology, lipid peroxide content, hepatosteatosis and inflammation obviously, as well as decreased the serum level of lipid and transaminases. Taken together, this study confirms that activation of the JNK/Sab signaling pathway-induced mitochondrial dysfunction plays a crucial role in the development of NASH. Scoparone can improve the lipotoxic liver injury partially by suppressing this signaling pathway, making it a potential therapeutic compound for NASH.

Effect of neoadjuvant iodine-125 brachytherapy upon resection of glioma.

BACKGROUND: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some patients miss the chance of surgical resection when the tumor involves critical structures. PURPOSE: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma. METHODS: Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bihemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery. RESULTS: Shrinkage of the tumor after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to everyday life with a KPS of 100. Another two patients had neurological injuries with KPSs of 80 and 50, respectively. One patient with grade II glioma died 34 months, and another with grade IV glioma died 40 months after the combined therapy. CONCLUSIONS: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.

Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.