Assessment of Left Ventricular Longitudinal Systolic Function Using Global Tissue Motion Annular Displacement in Patients with Chronic Severe Aortic Regurgitation.

Background: In patients with chronic aortic regurgitation (AR), the left ventricle (LV) develops compensatory mechanisms to sustain its function. LV global longitudinal strain (GLS) is a key means to detect subclinical LV dysfunction, even when LV ejection fraction (LVEF) remains within the normal range. Compared to GLS, Tissue motion annular displacement (TMAD) is a simpler strain-based method to assess LV systolic function. This study investigated the correlation among TMAD parameters, LVEF, and GLS, and determined the diagnostic value and threshold of TMAD parameters for left ventricular systolic dysfunction. Methods: A prospective study was conducted at a single center. The case and control groups consisted of patients with chronic severe AR and healthy volunteers, respectively. Speckle-tracking echocardiography (STE) was used to assess the GLS and TMAD parameters in the apical 4-chamber and apical 2-chamber. Subsets of participants were analyzed for inter- and intra-observer variability and analysis time. A correlation analysis was performed among the TMAD parameters, LVEF, and GLS. Receiver operating characteristic curves and the area under the curves (AUCs) were used to evaluate the predictive value of the TMAD parameters for LVEF <50% and GLS > -18%. Results: This study involved 96 patients with severe chronic AR and 45 healthy volunteers. Compared to GLS, TMAD demonstrated superior intra- and inter-observer consistency and shorter average analysis time. Biplane global Midpt% showed the highest correlation with GLS and LVEF among all the TMAD parameters, with r values of 0.81 and 0.74, respectively. Furthermore, global Midpt% had AUCs of 0.89 and 0.92 for predicting LVEF< 50% and GLS > -18%, respectively. Conclusion: The TMAD global Midpt% has the potential to replace GLS in clinical practice and find wide applications.

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies.

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.

Underlying Mechanisms of Brain Aging and Neurodegenerative Diseases as Potential Targets for Preventive or Therapeutic Strategies Using Phytochemicals.

During aging, several tissues and biological systems undergo a progressive decline in function, leading to age-associated diseases such as neurodegenerative, inflammatory, metabolic, and cardiovascular diseases and cancer. In this review, we focus on the molecular underpinning of senescence and neurodegeneration related to age-associated brain diseases, in particular, Alzheimer's and Parkinson's diseases, along with introducing nutrients or phytochemicals that modulate age-associated molecular dysfunctions, potentially offering preventive or therapeutic benefits. Based on current knowledge, the dysregulation of microglia genes and neuroinflammation, telomere attrition, neuronal stem cell degradation, vascular system dysfunction, reactive oxygen species, loss of chromosome X inactivation in females, and gut microbiome dysbiosis have been seen to play pivotal roles in neurodegeneration in an interactive manner. There are several phytochemicals (e.g., curcumin, EGCG, fucoidan, galangin, astin C, apigenin, resveratrol, phytic acid, acacetin, daucosterol, silibinin, sulforaphane, withaferin A, and betulinic acid) that modulate the dysfunction of one or several key genes (e.g., TREM2, C3, C3aR1, TNFA, NF-kb, TGFB1&2, SIRT1&6, HMGB1, and STING) affected in the aged brain. Although phytochemicals have shown promise in slowing down the progression of age-related brain diseases, more studies to identify their efficacy, alone or in combinations, in preclinical systems can help to design novel nutritional strategies for the management of neurodegenerative diseases in humans.

Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Beneficial effect of electroacupuncture on the distribution of foreign substances in the brain of rats developing depression-like behavior.

We used low and high molecular weight fluorescence tracers to investigate the entry of foreign solutes into the brain parenchyma and their exit from it by the glymphatic system, during experimentally induced depressive-like behavior in rats. The tail suspension test (TST), as an acute stressor, is known to induce such a type of behavior, considered to model the human major depressive disorder (MDD). Electroacupuncture (EAP) relieves both depressive-like behavior in rodents and the symptoms of MDD in humans. Here we report that 180 min after the intracisternal injection of the low molecular weight tracer Fluorescein-5-Isothiocianate Conjugated Dextran (FITC-d3), a 15-min duration TST tended to increase the control fluorescence in the brain of rats. Both EAP and sham EAP decreased the fluorescence of FITC-d3 in comparison with the TST, but not the control value. In addition, EAP and sham EAP counteracted the effects of TST. The high molecular weight tracer Ovalbumin Alexa Fluor 555 Conjugate (OA-45) failed to enter the brain parenchyma and accumulated at more superficial sites; however, EAP or sham EAP modified the distribution of fluorescence under TST application in a similar manner as that observed during the use of FITC-d3. It is concluded that EAP is possibly a valid treatment to slow down the entry of foreign solutes into the brain; in view of the comparable effects of EAP on FITC-d3 and OA-45 distribution, EAP seems to act before FITC-d3 passes the astroglial aquaporin-4 water channels, which are a critical constituent of the glymphatic system.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

[Discussion on the safety of acupuncture in experimental animals].

Many basic studies on acupuncture need to be carried out on experimental animals. However, the safety of acupuncture in experimental animals has been neglected for a long time. In the present paper, we make a discussion on the current situations, causes, its influence on research results and countermeasures of acupuncture safety events in experimental animals, so as to promote the safety evaluation of acupuncture in experimental animals and the standardized operation of acupuncture.

Effects of a calcium/vitamin D/Zinc combination on anti-osteoporosis in ovariectomized rats.

BACKGROUND: Osteoporosis is a major health problem in postmenopausal women, and characterized by deteriorated bone mass and micro-architecture. There have been some clinical trials demonstrating the beneficial effects of vitamin-D and some trace elements on calcium absorption and attenuation of osteoporosis development. However, effects of the combination of vitamin-D and zinc on calcium absorption and osteoporosis have not been adequately investigated. METHODS: Network pharmacology was first performed to explore possible correlations between calcium/vitamin D/zinc and osteoporosis. Forty-nine female Sprague-Dawley rats (6 months old, 250 ± 20 g) were randomized into 7 experimental groups with 7 animals per group for the in vivo study, including one sham surgery control group, one ovariectomizing (OVX) group, and 5 OVX plus treatment groups. At the end of animal experiment, animal tibia and femur leg bones and blood were collected for H&E staining, bone microstructure analysis by a micro-CT, measurement of bone and serum Ca, P and Zn concentrations, and immunohistochemical detection of macrophage-colony stimulating factor receptor (M-CSFR) and receptor activator of nuclear factor-kappa B ligand (RANKL). RESULTS: The network pharmacology analysis identified 57 candidate targets that were related to the osteoporosis-Ca/VitD/Zn interconnections. Further pathway analysis suggested that the combined treatment of Ca, VitD and Zn attenuated osteoporosis via modulation of metabolic pathways. We found that a therapy with Ca/VitD-M/Zn-M (73 mg/kg/day Ca, 0.6 g/kg/day VitD3 and 0.6 mg/kg/day zinc citrate) could significantly suppress the progression of osteoporosis in rats. After the Ca/VitD-M/Zn-M treatment, the ratio of bone volume/tissue volume, trabecular number and the trabecular thickness were all significantly elevated while the extent of trabecular separation was significantly reduced. Additionally, both serum calcium and bone calcium levels were significantly upregulated by the Ca/VitD/Zn treatment in a dose-dependent manner. The combination of Ca/VitD-M/Zn-M was superiou to either Ca/VitD-L/Zn-L or Ca/VitD-H/Zn-H treatment for such an effect. Moreover, the osteoporosis-associated M-CSFR and RANKL factors were both significantly downregulated by the Ca/VitD-M/Zn-M treatment in bone tissues of OVX rats. CONCLUSIONS: The combined supplement of VitD and Zn facilitates the Ca(2 +) absorption and attenuates the development of osteoporosis via down-regulation of osteoporosis-associated factors M-CSFR and RANKL, thus potentially constitutes an alternative therapy for the postmenopausal osteoporosis.

Effects of phosphorus application on yield, quality and phosphorus use efficiency of edible sweetpotato: A case study of Xushu 32.

To explore the appropriate amount of phosphorus (P) fertilizer and improve economic yield and P use efficiency of edible sweetpotato, we took Xushu 32 as an example and compared the effects of different P application rates on yield, quality, P accumulation and P use efficiency of edible sweetpotato based on a two-year field experiment (soil available P content was 31.70 mg·kg-1) from 2018 to 2019. There were five P application levels (P2O5), including 0 (P0), 25 (P25), 50 (P50), 75 (P75) and 100 kg·hm-2(P100). The results showed that, 1) compared with P0, P application significantly increased the yield of fresh sweetpotao and commodity potato, with the effects being the stongest under P75 treatment, followed by P50 treatment. However, there was no significant difference between the two treatments. 2) P application significantly increased the contents of starch and reducing sugar in storage root. The contents of soluble sugar and protein increased significantly under P50 treatment. 3) Du-ring the growth period of 90 to 120 d, P fertilizer supply significantly increased P accumulation and dry matter accumulation of sweetpotato. 4) The apparent P use efficiency (APUE) decreased with increasing P application rates, while P agronomic efficiency (PAE) increased first and then decreased with the increases of P application rates, which was significantly higher under P50 than other treatments. Taking into account the yield, quality, economic yield and P utilization rate of edible sweetpotato, the optimal dosage of P2O5 is 50 kg·hm-2 under the experimental conditions.

Consumption of fish oil high-fat diet induces murine hair loss via epidermal fatty acid binding protein in skin macrophages.

Fats are essential in healthy diets, but how dietary fats affect immune cell function and overall health is not well understood. Mimicking human high-fat diets (HFDs), which are rich in different fatty acid (FA) components, we fed mice various HFDs from different fat sources, including fish oil and cocoa butter. Mice consuming the fish oil HFD exhibit a hair-loss phenotype. Further studies show that omega-3 (n-3) FAs in fish oil promote atypical infiltration of CD207- (langerin-) myeloid macrophages in skin dermis, which induce hair loss through elevated TNF-α signaling. Mechanistically, epidermal fatty acid binding protein (E-FABP) is demonstrated to play an essential role in inducing TNF-α-mediated hair loss by activating the n-3 FA/ROS/IL-36 signaling pathway in dermal resident macrophages. Absence of E-FABP abrogates fish oil HFD-induced murine hair loss. Altogether, these findings support a role for E-FABP as a lipid sensor mediating n-3 FA-regulated macrophage function and skin health.

[Clinical observation of acupotomy combined with warm needling for cervical spondylotic radiculopathy of qi and blood stagnation syndrome].

OBJECTIVE: To observe the clinical effect of acupotomy combined with warm needling on cervical spondylotic radiculopathy (CSR) of qi and blood stagnation syndrome. METHODS: A total of 90 CSR patients were randomly divided into an acupotomy group, a warm needling group and a combined treatment group, with 30 cases in each group. The patients in the acupotomy group were treated with acupotomy, once every 7 days, consecutively for 3 times. The patients in the warm needling group received warm needling, once daily, at the interval of 2 days after consecutive treatments for 5 days, 7 days as one session of treatment and 3 consecutive sessions were required. The patients in the combined treatment group were treated with acupotomy and warm needling, and the methods and the treatment session were same as the the previous two groups. Before and after the treatment, the pain rating index (PRI) of McGill pain questionnaire (MPQ) and the 20-point scale of CSR developed by Yasuhisa Tanaka (CSR20) were adopted in the assessment. The changes of clinical symptoms and functions of patients were observed and the clinical efficacy was assessed in each group. RESULTS: After the treatment, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the 3 treatment groups when compared with those before the treatment. After the treatment, compared with the acupotomy group and the warm needling group, the PRI score was decreased (P<0.05) and the CSR20 score was increased (P<0.05) in the combined treatment group. The total effective rate was 83.3% (25/30) in the acupotomy group, 76.7% (23/30) in the warm needling group and 93.3% (28/30) in the combined treatment group. The total effective rate in the combined treatment group was higher than those in the acupotomy group and the warm needling group (P<0.05). CONCLUSION: The combined treatment with acupotomy and warm needling may obviously improve the clinical symptoms and physical signs, e.g. pain and numbness in the patients with CSR of qi and blood stagnation syndrome. Its efficacy is remarkably higher than that of the simple application of acupotomy or warm needling.

Clinical practice guidelines and expert consensus statements on rehabilitation for patients with COVID-19: protocol for a systematic review.

INTRODUCTION: COVID-19 is a highly infectious disease, characterised by respiratory, physical and psychological dysfunctions. Rehabilitation could effectively alleviate the symptoms and promote recovery of the physical and mental health of patients with COVID-19. Recently, rehabilitation medical institutions have issued clinical practice guidelines (CPGs) and expert consensus statements involving recommendations for rehabilitation assessments and rehabilitation therapies for COVID-19. This systematic review aims to assess the methodological quality and reporting quality of the guidance documents, evaluate the heterogeneity of the recommendations and summarise the recommendations with respect to rehabilitation assessments and rehabilitation therapies for COVID-19 to provide a quick reference for front-line clinicians, therapists and patients as well as reasonable suggestions for future guidelines. METHODS AND ANALYSIS: The electronic databases including PubMed, Embase, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Wanfang Database and China National Knowledge Infrastructure (CNKI) and websites of governments or organisations (eg, National Guideline Clearinghouse, Guidelines International Network, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network and WHO) will be searched for eligible CPGs and expert consensus statements from inception to August 2022. CPGs and expert consensus statements published in Chinese or English and presenting recommendations for modern functional rehabilitation techniques and/or traditional Chinese medicine rehabilitation techniques for COVID-19 will be included. Reviews, interpretations, old versions of CPGs and expert consensus statements and those for the management of other diseases during the pandemic will be excluded. Two reviewers will independently review each article, extract data, appraise the methodological quality following the Appraisal of Guidelines for Research & Evaluation II tool and assess the reporting quality with the Reporting Items for Practice Guidelines in Healthcare statement. The Measurement Scale of Rate of Agreement will be used to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements. Agreement between reviewers will be calculated using the intraclass correlation coefficient. We will also summarise the recommendations for rehabilitation in patients with COVID-19. The results will be narratively described and presented as tables or figures. ETHICS AND DISSEMINATION: Ethics approval is not needed for this systematic review because information from published documents will be used. The findings will be submitted for publication in a peer-reviewed journal and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PROSPERO REGISTRATION NUMBER: CRD42020190761.

[To explore mechanism of Scabiosa comosa against liver fibrosis based on pharmacodynamics and network pharmacology].

This study aims to systematically elucidate the pharmacodynamics and network pharmacological mechanism of Mongolian medicinal plants Scabiosa comosa, explore their key targets and related pathways, and further clarify the mechanism of the plants in treating liver fibrosis. Wistar rats were assigned into the blank group, carbon tetrachloride-induced liver fibrosis model group, and low-, medium-, and high-dose S. comosa groups. HE staining and Masson staining were performed for the observation of liver tissue under a microscope. Further, Wistar rats were assigned into a control group and a S. comosa group for administration. Seven days later, blood was collected from the abdominal aorta, and different doses of drug-containing serum samples were used to treat hepatic stellate cell-T6(HSC-T6). Flow cytometry was adopted to detect the apoptosis of HSC-T6 cells. Ultra-high performance liquid chromatography-time of flight-mass spectrometry(UHPLC-TOF-MS) was employed to determine the components in Scabiosa comosa. The target of S. comosa and liver fibrosis were obtained from SwissTargetPrediction and GeneCards, respectively, and the common targets were selected as the anti-liver fibrosis targets. Protein-protein interaction was analyzed via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out via Metascape. Phosphatidylinosital 3-kinase(PI3 K), protein kinase B(AKT), p-AKT, p38, and p-p38 targets which are involved in the top-ranked PI3 K/AKT and mitogen activated kinase-like protein(MAPK) signaling pathways were selected for validation via Western blot. The HE and Masson staining results showed that Scabiosa alleviated the hyperplasia of connective tissue and the fibrosis. The serum containing Scabiosa significantly promoted the apoptosis of HSC-T6 in a concentration-dependent manner. A total of 76 chemical components were identified by UHPLC-TOF-MS, among which flavonoids, alkaloids, terpenoids, phenols, and fatty acids were the main components. According to the prediction, there were 63 anti-liver fibrosis targets in Scabiosa comosa, the annotated GO terms of which involved biological processes, cell components, and molecular functions. The KEGG pathway enrichment showed that the targets were mainly involved in PI3 K/AKT, epidermal growth factor receptor(EGFR), RAS-associated protein 1(Rap1), hypoxia-inducible factor 1(HIF-1), resistance to audiogenic seizures(Ras), and MAPK signaling pathways. Western blot results showed that compared with the model group, S. comosa down-regulated the protein levels of α-smooth muscle actin(α-SMA), collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in liver tissue. Compared with the control group, the low-, medium-, and high-dose S. comosa significantly down-regulated the protein levels of α-SMA, collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in HSC-T6. The evidence of pharmacodynamics, network pharmacology, and molecular biology indicated that the plants of S. comosa had significant activity against liver fibrosis, the mechanism of which may involve the regulation of the key targets PI3 K, AKT, and MAPK14 p38 in the PI3 K/AKT and MAPK signaling pathways.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta. RESULTS: EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects. CONCLUSION: EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

[Effect of balance acupotomy combined with warm needling in treatment of cervical spondylosis of vertebral artery type].

OBJECTIVE: To observe the clinical efficacy of balance acupotomy combined with warm needling in treatment of cervical spondylopathy of vertebral artery type (CSA). METHODS: Ninety patients were randomly divided into a warm needling group, a balance acupotomy group and a combined treatment group, 30 cases in each one. In the warm needling group, warm needling was given, once daily, for 5 days consecutively, with the interval of 2 days every week, and the treatment was conducted for 3 weeks. In the combined treatment group, on the base of the treatment as the warm needling group, the balance acupotomy was exerted, for consecutive 3 weeks. In the balance acupotomy group, the balance acupotomy was adopted, once a week, for 3 weeks consecutively. Clinical efficacy, the mean blood flow velocity of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA), the pulse index (PI) and the resistance index (RI) were observed in 3 groups separately. The score of vertigo symptom and function was compared before and after treatment in 3 groups. RESULTS: In comparison with before treatment, the score of evaluation scale for cervical vertigo (ESCV) and the mean blood flow velocity of LVA, RVA and BA were all increased (P<0.05). while PI and RI reduced (P<0.05) in each group after treatment. In comparison with those in the warm needling group and the balance acupotomy group, ESCV score and the mean blood flow velocity of LVA, RVA and BA were increased (P<0.05), while PI and RI decreased (P<0.05) in the combined treatment group after treatment. Compared with the balance acupotomy group, the mean blood flow velocity of LVA, RVA and BA was increased (P<0.05), and PI and RI reduced (P<0.05) in the warm needling group after treatment. The total effective rate was 73.3% (22/30) in the warm needling group, 70.0% (21/30) in the balance acupotomy group and 93.3% (28/30) in the combined treatment group respectively. The total effective rate in the combined treatment group was higher than that either in the warm needling group or in the balance acupotomy group (P<0.05). CONCLUSION: Balance acupotomy combined with warm needling may restore the mechanical equilibrium state of the neck, and effectively improve the change of vertebral-basilar artery blood flow and relieve vertigo symptoms in patient with of cervical spondylosis of vertebral artery type.

Silver-catalysed three-component reactions of alkynyl aryl ketones, element selenium, and boronic acids leading to 3-organoselenylchromones.

An Ag-catalysed three-component reaction of alkynyl aryl ketones bearing an ortho-methoxy group, element selenium, and arylboronic acid, providing a facile route to selenofunctionalized chromone products has been developed. This protocol features high efficiency and high regioselectivity, and the use of selenium powder as the selenium source. Mechanistic experiments indicated that the combined oxidative effect of (bis(trifluoroacetoxy)iodo)benzene and oxygen in the air pushes the catalytic redox cycle of the Ag catalyst and the phenylselenium trifluoroacetate formed in situ is the key intermediate of the PIFA-mediated 6-endo-electrophilic cyclization and selenofunctionalization reaction of alkynyl aryl ketones.

Intensifying Upconverted Ultraviolet Emission towards Efficient Reactive Oxygen Species Generation.

Multiphoton upconversion that can convert near-infrared irradiation into ultraviolet emission offers many unique opportunities for photocatalysis and phototherapy. However, the high-lying excited states of lanthanide emitters are often quenched by the interior lattice defects and deleterious interactions among different lanthanides, resulting in weak ultraviolet emission. Here, we describe a novel excitation energy lock-in approach to boost ultraviolet upconversion emission in a new class of multilayer core-shell nanoparticles with a gadolinium-rich core domain. Remarkably, we observe more than 70-fold enhancements in Gd3+ emission from the designed nanoparticles compared with the conventional nanoparticles. Our mechanistic investigation reveals that the combination of energy migration over the core domain and optically inert NaYF4 interlayer can effectively confine the excitation energy and thus lead to intense multiphoton ultraviolet emission in upconversion nanostructures. We further achieve a 35.6% increase in photocatalytic reactivity and 26.5% in reactive oxygen species production yield in ZnO-coated upconversion nanocomposites under 808-nm excitation. This study provides a new insight to energy transfer mechanism in lanthanide-doped nanoparticles and offers an exciting avenue for exploring novel near-infrared photocatalysts.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants: a meta-analysis.

BACKGROUND: The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants is not known. Thus, we conducted a meta-analysis to identify any prevention effect. METHODS: PubMed, EMBASE, and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants. Revman 5.3 was used to synthesize the results. A fixed-effect model was used to summarize the data when the heterogeneity was non-significant (I2 < 50%), and a random-effects model was used when the heterogeneity was significant (I2 > 50%). RESULTS: Of 728 articles, 11 randomized controlled trials met the inclusion criteria. The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio (RR) = 0.53, 95% confidence interval (CI) 0.36-0.80, P = 0.002. The heterogeneity was non-significant with I2 = 23%. Subgroup analysis based on parenteral nutrition duration and median birth weight was performed. The synthesis results for patients with parenteral nutrition duration exceeding 14 days revealed I2 = 35% (P = 0.15) and pooled RR = 0.47, 95% CI 0.30-0.73, P = 0.0008; and for patients with duration less than 14 days revealed I2 = 0% (P = 0.72) and pooled RR = 1.14, 95% CI 0.39-3.35, P = 0.81. The synthesis for patients with birth weight more than 1000 g revealed I2 = 0% (P = 0.41) and pooled RR = 0.55, 95% CI 0.26-1.18, P = 0.12; and for patients with birth weight below 1000 g revealed I2 = 44% (P = 0.11) and pooled RR = 0.53, 95% CI 0.33-0.85, P = 0.009. CONCLUSIONS: The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the available original randomized controlled trial studies, especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants. Future studies should be performed before a definitive conclusion can be established.

The effects of acupuncture therapy in migraine: An activation likelihood estimation meta-analysis.

Background: Previous functional magnetic resonance imaging studies indicated that acupuncture could activate the brain regions in patients with migraine. However, these studies showed inconsistent results. This activation likelihood estimation (ALE) meta-analysis aimed to investigate the consistent activated change of brain regions between pre- and post-acupuncture treatment in migraineurs. Methods: We conducted a literature search in PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang Database, and the Chinese Biomedical Literature Database from their inception to 18 August, 2022, to obtain articles assessing the functional magnetic resonance imaging changes of acupuncture for migraine. Two investigators independently performed literature selection, data extraction, and quality assessment. The methodological quality was assessed with a modified version of the checklist. The reporting quality of interventions among included studies was evaluated by the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Our meta-analysis was conducted according to the GingerALE software. The Jackknife sensitivity analysis was used to assess the robustness of the results. Results: 14 articles were finally included according to the eligible criteria. Regarding the immediate effect of acupuncture on migraine, the ALE meta-analysis demonstrated that the deactivation regions were mainly located in the superior frontal gyrus, and middle frontal gyrus (uncorrected P < 0.001). The ALE meta-analysis of the cumulative effect showed that the activation regions were the thalamus, superior frontal gyrus, posterior lobe of the cerebellum, insula, middle frontal gyrus, precentral gyrus, anterior cingulate, and the deactivation brain regions were located in the transverse temporal gyrus, postcentral gyrus, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, inferior parietal lobule, and inferior occipital gyrus (uncorrected P < 0.001). Conclusion: Acupuncture could activate multiple brain areas related with the regulation of pain conduction, processing, emotion, cognition, and other brain regions in patients with migraine. In the future, the combination of multiple imaging technologies could be a new approach to deeply investigate the central mechanism of acupuncture for migraine.

Acupuncture for tension-type headache: a systematic review and meta-analysis of randomized controlled trials.

Background: Tension-type headache (TTH) is the most common neurologic disease worldwide. Acupuncture is commonly applied to treat TTH, but evidence of acupuncture for TTH is contradictory based on previous meta-analyses. Therefore, we conducted this systematic review and meta-analysis to update the evidence of acupuncture for TTH and aimed to provide a valuable reference for clinical application. Methods: We searched 9 electronic databases from their inceptions to July 1, 2022 for randomized controlled trials (RCTs) of acupuncture for TTH. We also manually searched reference lists and relevant websites, and the experts in this field were consulted for possible eligible studies. Two independent reviewers conducted literature screening, data extraction, and risk of bias assessment. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias of included studies. Subgroup analyses were carried out based on frequency of acupuncture, total sessions, treatment duration, needle retention, types of acupuncture and categories of medication. Data synthesis was performed using Review Manager 5.3 and Stata 16. The Grading of Recommendations Assessment, Development and Evaluation Approach (GRADE) was used to evaluate the certainty of evidence of each outcome. Meanwhile, the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) was used to assess the reporting quality of interventions in clinical trials of acupuncture. Results: 30 RCTs involving 2,742 participants were included. According to ROB 2, 4 studies were considered as low risk, and the rest studies were some concerns. After treatment, compared with sham acupuncture, acupuncture had greater effect in improvement of responder rate [3 RCTs, RR = 1.30, 95%CI (1.13, 1.50), I2 = 2%, moderate certainty] and headache frequency [5 RCTs, SMD = -0.85, 95%CI (-1.58, -0.12), I2 = 94%, very low certainty]. In contrast to medication, acupuncture was more effective to reduce pain intensity [9 RCTs, SMD = -0.62, 95%CI (-0.86, -0.38), I2 = 63%, low certainty]. Adverse events were evaluated in 16 trials, and no serious event associated with acupuncture occurred. Conclusions: Acupuncture may be an effective and safe treatment for TTH patients. Due to low or very low certainty of evidence and high heterogeneity, more rigorous RCTs are needed to verify the effect and safety of acupuncture in the management of TTH.