Automated insulin delivery in children with type 1 diabetes during physical activity: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.

Shenmai Injection Alleviates Myocardial Ferroptosis via Activating the AKT1/mTOR Pathway in Rats with Acute Myocardial Infarction.

OBJECTIVE: Acute myocardial infarction (AMI) poses a serious burden on public health. Shenmai Injection (SMI) has been reported to have a cardioprotective effect and is used clinically attributed to its targeting of ferroptosis. This study aims to explore the underlying mechanisms of SMI in treating AMI through the application of network pharmacology analysis. METHODS: This study utilized network pharmacology to identify the bioactive ingredients and potential targets of SMI in treating AMI. A rat model of AMI was created by ligating the coronary arteries of rats, and a cell model was established by subjecting H9c2 cells to oxygen-glucose deprivation (OGD) to reveal the cardioprotective effects of SMI. Western blotting was employed to measure protein expressions, while hematoxylin-eosin staining was used to observe relevant pathological changes. Enzyme linked immunosorbent assay was conducted to measure the levels of biomarkers associated with cardiac injury and oxidative stress. RESULTS: A comprehensive analysis revealed a total of 225 putative targets of SMI in the context of AMI which exerted regulatory effects on numerous pathways and targeted multiple biological processes. AKT1 was identified as a core target mediating the effects of SMI on AMI by topological analysis. In vivo experiments revealed that SMI attenuated myocardial injury, oxidative stress, and ferroptosis in rats with AMI. Furthermore, SMI was found to enhance the expression levels of p-AKT1 and p-mTOR proteins in the myocardial tissues of rats afflicted with AMI. Similar findings were also observed in H9c2 cells subjected to OGD. Of particular interest, the suppression of OGD-induced iron accumulation, oxidative stress, and ferroptosis-associated proteins by SMI in H9c2 cells was reversed upon inhibition of the AKT1/mTOR pathway via MK2206. CONCLUSION: This study revealed that SMI exerts a protective effect against myocardial injury and ferroptosis caused by AMI via the activation of the AKT1/mTOR pathway.

Machine Learning Maps Research Needs in COVID-19 Literature.

As of August 2020, thousands of COVID-19 (coronavirus disease 2019) publications have been produced. Manual assessment of their scope is an overwhelming task, and shortcuts through metadata analysis (e.g., keywords) assume that studies are properly tagged. However, machine learning approaches can rapidly survey the actual text of publication abstracts to identify research overlap between COVID-19 and other coronaviruses, research hotspots, and areas warranting exploration. We propose a fast, scalable, and reusable framework to parse novel disease literature. When applied to the COVID-19 Open Research Dataset, dimensionality reduction suggests that COVID-19 studies to date are primarily clinical, modeling, or field based, in contrast to the vast quantity of laboratory-driven research for other (non-COVID-19) coronavirus diseases. Furthermore, topic modeling indicates that COVID-19 publications have focused on public health, outbreak reporting, clinical care, and testing for coronaviruses, as opposed to the more limited number focused on basic microbiology, including pathogenesis and transmission.

Wrist-ankle acupuncture and Fluoxetine in the treatment of post-stroke depression: a randomized controlled clinical trial.

OBJECTIVE: To investigate the effects of WAA combined with fluoxetine in the clinical treatment of post-stroke depression (PSD) . METHODS: In this randomized, controlled and single-blind trial, 105 PSD patients who met the inclusion criteria were randomly divided into three equal groups: Thin wrist-ankle acupuncture (WAA) group (Thin WAA needle + Fluoxetine), Thick WAA group (Thick WAA needle + Fluoxetine), and Sham WAA group (sham WAA needle + Fluoxetine). In this trial, the primary outcome was Hamilton Depression Scale (HAMD), while the secondary outcomes included Zung self-rating depression scale (SDS) and World Health Organization Quality of Life BREF (QQL). RESULTS: Ninety nine PSD patients completed all the treatment. The HAMD scores and SDS scores of all the three groups decreased after treatment (P < 0.05); thick WAA group and thin WAA group decreased more obviously than the sham WAA group (P < 0.05). There was no significant difference between the QQL scores of the three groups (P > 0.05). There was no significant difference in the scores of the three scales between the thick wrist ankle needles and the thin wrist ankle needles (P > 0.05). CONCLUSION: The present study showed that WAA combined with fluoxetine can relieve the symptoms of depression after stroke. WAA therapy could improve the antidepressant effect of fluoxetine.

[Fire needling on dysphagia due to pseudobulbar palsy after stroke: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of fire needling on dysphagia due to pseudobulbar paralysis after stroke and to compare the difference in clinical effect between fire needling and swallowing function rehabilitation training. METHODS: A total of 76 patients with dysphagia due to pseudobulbar paralysis after stroke were randomly divided into an observation group and a control group, 38 cases in each group (1 case dropped out in the control group). The both groups were based on conventional western medication treatment. Fire needle pricking was exerted at Lianquan (CV 23), Fengchi (GB 20), Wangu (GB 12), Shuigou (GV 26), Neiguan (PC 6) and Zusanli (ST 36) without needle retaining every other day in the observation group. The control group was treated with the swallowing function rehabilitation training. In both groups, treatment for 2 weeks was as one course and 2 courses of treatment with 2-day interval were required. After treatment, swallowing scores of Fujishima Ichiro and swallow quality of life questionnaire (SWAL-QOL) scores were observed in both groups, and the clinical effect was compared. Follow-up of swallowing scores of Fujishima Ichiro in 4 weeks after treatment was completed to evaluate the clinical effect. RESULTS: The clinical effective rates after treatment and follow-up were 92.1% (35/38) and 94.7% (36/38) in the observation group, higher than 75.7% (28/37) and 83.8% (31/37) in the control group (P<0.05). After treatment, the swallowing scores of Fujishima Ichiro and SWAL-QOL scores were increased in the two groups (P<0.05), and those in the observation group were higher than the control group (P<0.05). The swallowing scores of Fujishima Ichiro were increased during follow-up in the two groups (P<0.05). CONCLUSION: Fire needling has a better effect than conventional rehabilitation training in the treatment of dysphagia due to pseudobulbar paralysis after stroke, which can obviously improve the swallowing function and quality of life in patients with dysphagia.

Efficacy and safety of electroacupuncture on treating depression-related insomnia: a study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Sleep disorders including insomnia occur frequently in depressive patients. Acupuncture is a widely recognised therapy to treat depression and sleep disorders in clinical practice. This multicentre randomised controlled trial (RCT) is aimed to investigate the efficacy and safety of electroacupuncture (EA) in the treatment of depression patients with insomnia. METHODS AND ANALYSIS: We describe a protocol for a multicentre RCT. A total of 270 eligible patients in three different healthcare centres in Shanghai will be randomly assigned to one of these three groups: treatment group (EA + standard care), control A group (sham electroacupuncture + standard care) and control B group (standard care). Treatment will be given three times per week for 8 consecutive weeks. The primary outcome is the Pittsburgh Sleep Quality Index. The secondary outcomes are sleep parameters recorded in the actigraphy, Hamilton Rating Scale for Depression score and Self-rating Anxiety Scale score. Daily dose of patients' antidepressant and sedative-hypnotic medication will be recorded in the dairy. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, 4 weeks post-treatment and 8 weeks post-treatment, as well as at 1-month, 3-month and 6-month follow-up. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2017SHL-KY-04). Written informed consent will be obtained from all participants. The results of this study will be published in peer-reviewed journals or presented at academic conferences. TRIAL REGISTRATION NUMBER: NCT03122080; Pre-results.

Acupuncture relieves motion sickness via the IRß-ERK1/2-dependent insulin receptor signalling pathway.

OBJECTIVE: Acupuncture has been widely used for the treatment of motion sickness (MS), but the underlying mechanisms are unclear. The aim of this research was to study the mechanism of acupuncture in the treatment of MS. METHODS: To observe the effects of acupuncture in the treatment of MS, 80 rats were randomised into five groups that were subjected to acceleration and either remained untreated (CTRL), or received restraint (REST), scopolamine (SCOP) or acupuncture at SP4 (sham) or PC6+ST36 (verum) acupuncture points. To study the mechanism underlying the effects of acupuncture in the treatment of MS, 48 rats were randomised into three groups: acupuncture+extracellular regulated protein kinases (ERK) 1/2 inhibitor (ERKinh), acupuncture+insulin receptor (IR) antagonist (IRant), and acupuncture+vehicle (VEH). After acceleration, the MS index (MSI) and spontaneous activity (SA) of the rats were recorded. Serum stress hormones, Fos-positive cells, c-fos mRNA in the vestibular nucleus, and IRß-, p-IRß-, ERK1/2- and p-ERK1/2-positive cells in the dorsal motor nucleus of the vagus nerve (DMV) were detected. RESULTS: After acceleration, MS symptoms in the PC6+ST36 and SCOP groups were reduced compared with the CTRL, REST, and SP4 groups. The number of p-IRß- and p-ERK1/2-positive cells and insulin levels were higher in the PC6+ST36 group than in the CTRL, REST, and SP4 groups. After ERK1/2 inhibitor and IR antagonist treatment, MS symptoms in the VEH group were lower than in the ERKinh and IRant groups. CONCLUSIONS: Our study demonstrates that acupuncture significantly alleviates MS through the IRß-ERK1/2-dependent insulin receptor signalling pathway in the DMV.

Targeting TNFα Ameliorated Cationic PAMAM Dendrimer-Induced Hepatotoxicity via Regulating NLRP3 Inflammasomes Pathway.

Hepatotoxicity of cationic poly amidoamine (PAMAM) dendrimers is one of the most urgent challenges to their medicinal application. Recent studies have indicated that proinflammatory cytokines were critical in nanomaterials-induced toxicity. However, little is known about the roles and underlying regulatory mechanisms of proinflammatory cytokines in cationic PAMAM dendrimer-induced hepatotoxicity. Thus, the aim of the current study was to explore the role of proinflammatory cytokine tumor necrosis factor alpha (TNFα) in cationic PAMAM dendrimer-induced liver injury and its underlying mechanism and develop novel strategies to reduce hepatotoxicity of cationic PAMAM dendrimers through regulating TNFα. In this study, we verified the significant overexpression of TNFα in cationic PAMAM dendrimer-induced hepatotoxicity in mice and found that targeting TNFα by etanercept could protect against cationic PAMAM dendrimer-induced liver injury. Interestingly, etanercept suppressed cationic PAMAM dendrimer-induced inflammasome signaling as demonstrated by reduced activation of NALP3, cleavage of Caspase-1, and maturation of interleukin (IL)-1ß. Moreover, suppression of NLRP3 inflammasomes by belnacasan could also protect against cationic PAMAM dendrimer-induced hepatotoxicity and TNFα-induced acute hepatotoxicity. Notably, targeting either TNFα or inflammasomes reduced autophagy activation in hepatotoxicity triggered by cationic PAMAM dendrimers. In general, these findings revealed that targeting TNFα could ameliorate cationic PAMAM dendrimer-induced hepatotoxicity via regulating NLRP3 inflammasome pathway, underscoring that TNFα antagonism by etanercept could be used as an effective pharmacological approach to control hepatotoxicity of cationic PAMAM dendrimers and thus providing novel therapeutic strategies for managing liver toxicity of nanomaterials via regulating inflammatory mediators.

Electroacupuncture Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis.

Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed. Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats. Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis. Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h. Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death.

Poly-amidoamine (PAMAM) dendrimers are proposed to be one of the most promising drug-delivery nanomaterials. However, the toxicity of PAMAM dendrimers on the central nervous system seriously hinders their medical applications. The relationship between oxidative stress and autophagy induced by PAMAM dendrimers, and its underlying mechanism remain confusing. In this study, we reported that PAMAM dendrimers induced both reactive oxygen species and autophagy flux in neuronal cells. Interestingly, autophagy might be triggered by the formation of reactive oxygen species induced by PAMAM dendrimers. Suppression of reactive oxygen species could not only impair PAMAM dendrimers-induced autophagic effects, but also reduce PAMAM dendrimers-induced neuronal cell death. Moreover, inhibition of autophagy could protect against PAMAM dendrimers-induced neuronal cell death. These findings systematically elucidated the interplay between oxidative stress and autophagy in the neurotoxicity of PAMAM dendrimers, which might encourage the application of antioxidants and autophagy inhibitors to ameliorate the neurotoxicity of PAMAM dendrimers in clinic.

Wrist-ankle acupuncture (WAA) for precompetition nervous syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Precompetition nervous syndrome comprises an excessive nervous and anxiety response to the high-pressure environment preceding a sporting competition. The use of acupuncture as a treatment option for anxiety, and wrist-ankle acupuncture (WAA) specifically in this instance, has been identified as a growing trend within the Western world. In our previous study, we have confirmed the efficacy of WAA for pre-examination anxiety. In this paper, we present a randomized controlled single-blind trial evaluating the use of WAA for precompetition nervous syndrome, comparing it with the intervention of sham acupuncture. METHODS/DESIGN: The study was designed as a randomized controlled single-blind trial to evaluate the effects of WAA for precompetition anxiety. The trial will be conducted in annual track and field events of Shanghai University of Sport. A total of 100 participants who meet inclusion criteria are randomly assigned by computerized randomization to receive WAA therapy or sham acupuncture. The group allocations and interventions are concealed to participants and statisticians. The Competition State Anxiety Scale (CSAI-2) is used as the primary outcome measure, while heart rate, blood pressure, respiratory frequency, tension syndrome curative effect evaluation and participants' feeling of acupuncture questionnaire are applied as secondary outcome measures. DISCUSSION: The results of this trial will confirm whether WAA is effective to treat precompetition anxiety in annual track and field events. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-13003931; registration date: 22 October 2013).

Traditional Chinese Acupuncture for Poststroke Depression: A Single-Blind Double-Simulated Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and possible side-effect of treating poststroke depression patients by traditional Chinese body acupuncture. DESIGN: Single-blind double-simulated randomized controlled trial. SETTING: Inpatient wards of neurology and rehabilitation departments. PARTICIPANTS: Sixty-eight (68) participants who met the criteria were randomly assigned into two groups, 34 cases (32 completed) into intervention group and 34 cases (33 completed) into control group. INTERVENTIONS: Body acupuncture (Shuigou GV 26, Neiguan PC 6, and Zusanli ST 36) and oral placebo were used in intervention group while fluoxetine and minimal nontraditional acupuncture (minimally active penetrating) were used in control group. Patients in both groups were treated separately once a day for 6 weeks. OUTCOME MEASURES: Outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), and side-effects were measured using the Side Effect Rating Scale (SERS) of Asberg and a self-designed needling adverse events scale. Clinical effects of both groups were statistically valued before treatment, week-2, week-6, and month-3. RESULTS: The total curative effects of both groups are similar (p > 0.05; evaluated in week-6 and month-3), while intervention group had an earlier onset time at week-2 (p < 0.05). The intervention group has fewer side-effects in week-2 (p < 0.05). CONCLUSIONS: Body acupuncture was effective in reducing stroke patients' depressive symptoms and had fewer side-effects. It should be considered as an option for neuropsychiatric sequelae of stroke.

Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in hepatocellular carcinoma cells.

Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.

Suppression of autophagy enhanced growth inhibition and apoptosis of interferon-ß in human glioma cells.

Interferon-beta (IFN-ß) is a cytokine with anti-viral, anti-proliferative, and immunomodulatory effects. In this study, we investigated the effects of IFN-ß on the induction of autophagy and the relationships among autophagy, growth inhibition, and apoptosis induced by IFN-ß in human glioma cells. We found that IFN-ß induced autophagosome formation and conversion of microtubule associated protein 1 light chain 3 (LC3) protein, whereas it inhibited cell growth through caspase-dependent cell apoptosis. The Akt/mTOR signaling pathway was involved in autophagy induced by IFN-ß. A dose- and time-dependent increase of p-ERK 1/2 expression was also observed in human glioma cells treated with IFN-ß. Autophagy induced by IFN-ß was suppressed when p-ERK1/2 was impaired by treatment with U0126. We also demonstrated that suppression of autophagy significantly enhanced growth inhibition and cell apoptosis induced by IFN-ß, whereas inhibition of caspase-dependent cell apoptosis impaired autophagy induced by IFN-ß. Collectively, these findings indicated that autophagy induced by IFN-ß was associated with the Akt/mTOR and ERK 1/2 signaling pathways, and inhibition of autophagy could enhance the growth inhibitory effects of IFN-ß and increase apoptosis in human glioma cells. Together, these findings support the possibility that autophagy inhibitors may improve IFN-ß therapy for gliomas.