A Straightforward Approach to Fluorinated Pyrimido[1,2-b]indazole Derivatives via Metal/Additive-Free Annulation with Enaminones, 3-Aminoindazoles, and Selectfluor.

A novel and efficient three-component reaction with two C-N bonds and one C-F bond formation has been reported, which provides a straightforward route to a variety of fluorinated pyrimido[1,2-b]indazole derivatives. This transformation has the advantage of excellent functional group compatibility, including aliphatic and aromatic substituents enaminones. Moreover, metal and additives are not necessary for this reaction, which is of great significance for the synthesis and application of fluorinated heterocycles.

Motor function and fALFF modulation in convalescent-period ischemic stroke patients after scalp acupuncture therapy: a multi-centre randomized controlled trial.

BACKGROUND: Scalp acupuncture has been found to be effective at improving motor function after ischemic stroke, but few studies examining its central mechanisms of action have been carried out. The aim of this study was to investigate the clinical effects of scalp acupuncture on motor dysfunction and changes in spontaneous brain activity in patients with ischemic stroke. METHODS: This was an evaluator- and analyst-blinded, multi-center randomized controlled trial. A total of 108 convalescent-stage ischemic stroke patients with motor dysfunction were allocated to receive either scalp acupuncture combined with rehabilitation treatment (SR group) or rehabilitation treatment alone (RE group). Patients in both groups received treatment 5 times per week for 8 weeks. The primary outcome measure was the Fugl-Meyer assessment (FMA). Secondary outcome measures included the modified Barthel index (mBI), modified Rankin scale (mRS) and values of fractional amplitude of low frequency fluctuation (fALFF) acquired using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. RESULTS: Both groups showed significant improvements in motor function, daily life ability and degree of disability, as measured by FMA, mRS and mBI (p < 0.05), and the SR group showed a significantly greater improvement (p < 0.05). Compared with the RE group, the areas where the fALFF values increased in the SR group were located in the cerebellum, praecuneus, precentral gyrus, superior frontal gyrus and parietal lobe. The improvement in FMA scores had the strongest correlation with the baseline fALFF values of the ipsilateral precentral gyrus. CONCLUSION: Scalp acupuncture improved motor function in convalescent-period ischemic stroke patients, and effects were correlated with regulation of motor-relevant brain regions. The fALFF value of the ipsilateral precentral and postcentral gyri could be potential clinical indices for prognostication of motor dysfunction. TRIAL REGISTRATION NUMBER: NCT03120650 (http://www.clinicaltrials.gov).

Acupuncture for migraine prophylaxis: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Migraine causes health problems in 1 billion people worldwide and imposes a huge social burden. Acupuncture therapy has a good clinical effect in migraine prophylaxis and is recommended by authoritative journals. We plan to conduct a Bayesian network meta-analysis to compare the efficacies of different acupuncture therapies. METHODS: We will search PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database for Chinese technical periodicals, Chinese biological medical database, WanFang Data, Cochrane register of controlled trials, Chinese Clinical Trial Register, and ClinicalTrials.gov from their inception to July 1, 2022, for randomized controlled trials that studied different acupuncture therapies and other therapies for the preventive treatment of migraine. Migraine episodes, migraine days, headache intensity, and adverse events will be counted as outcomes. Two reviewers will independently complete the study selection, data extraction, and risk of bias assessment of all filtered trials. Pairwise meta-analysis and Bayesian network meta-analysis will be performed (if applicable) through Review Manager 5.3 and the "gemtc" and "rjags" packages of the R software. Confidence in Network Meta-Analysis will be used to evaluate the quality and credibility of the evidence for each outcome. RESULTS: The protocol will compare the efficacies of different acupuncture therapies for migraine prophylaxis. CONCLUSION: This study aims to help clinicians develop an effective and safe treatment plan for migraine prophylaxis.

[Electroacupuncture at Siguan points for migraine of liver yang hyperactivity: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity. METHODS: A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups. RESULTS: After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (ï¼°<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (ï¼°<0.05). After treatment, the migraine symptom scores in the two groups were decreased (ï¼°<0.05), the change in the electroacupuncture group was greater than the western medication group (ï¼°<0.05). CONCLUSION: Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.

Cytoplasm or Supernatant: Where Is the Treasury of the Bioactive Antiaging Factor from Mesenchymal Stem Cells?

Cell-free compounds of mesenchymal stem cells (MSCs) could be a safer and cheaper substitution for MSC transplantation and have gained substantial research interest for antiaging skin treatments. However, whether those bioactive components should be obtained from the cytoplasm or supernatant is yet to be determined. In this study, we examined the ingredients of the MSC cytoplasm extract (MSC-ex) and MSC supernatant (MSC-s) and evaluated their effect in a photoaging model. Although MSC-ex has a richer protein composition than MSC-s, the latter has a proteome associated with wound healing and blood vessel development. Over 85% of the proteins in MSC-s were also found in MSC-ex, including extracellular matrix protein and various growth factors. The results of real-time PCR and western blot also demonstrate that both MSC-s and MSC-ex can upregulate collagen, transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF) and downregulate IL-1ß and matrix metalloproteinase-1 (MMP-1), which were considered critical for antiphotoaging. This supports our observations in the Hematoxylin and Eosin (HE) and Masson staining assay that they have a comparable effect as MSCs in terms of enhancing dermal thickness, and stimulating collagen regeneration. Although MSC-s and MSC-ex showed a weaker immunosuppression effect than MSCs, moisture measurement showed that they repair damage more rapidly than MSCs. Furthermore, the histological results showed that MSC-s maintains a super effect on immunosuppression, epidermal repair, and angiogenesis. That may be associated with the higher content of laminin, TGF-ß, and VEGF in MSC-s, as well as its super cytokine transcriptional regulation ability. Thus, both MSC-s and MSC-ex can safely and effectively promote the repair of skin light injury, similar to MSCs. Our findings can broaden the range of active factors available in cell-free treatment, determine the difference between MSC-s and MSC-ex, and provide a reference for the development of similar products in regenerative medicine.

Mediating effect of lower extremity muscle strength on the relationship between mobility and cognitive function in Chinese older adults: A cross-sectional study.

Aging is a multifactorial process associated with irreversible decline in mobility and cognitive function. However, the mechanisms underlying the relationship between mobility and cognitive function remain elusive. In specific, the mediating effect of muscle strength, which is essential to maintain mobility, on this relationship has yet to be clarified. Accordingly, we performed a cross-sectional study involving Chinese older adults to understand the role of muscle strength in the relationship between mobility and cognitive function. The cognitive function and physical performance of 657 community-dwelling participants aged over 65 years old were observed. Cognitive function was assessed using the Mini-Mental State Examination, whereas physical performance, including mobility and muscle strength, was measured via Timed Up-and-Go Test and knee extension strength measurement. Data were statistically analyzed using PROCESS Model 4 developed by Hayes, and 595 complete data were finally included. Physical performance (mobility and muscle strength) was significantly correlated with cognitive function (p < 0.01). Muscle strength was negatively correlated with mobility (r = -0.273, p < 0.001) and positively correlated with cognitive function (r = 0.145, p < 0.001). Muscle strength accounted for 20.1% of the total mediating effects on the relationship between mobility and cognitive function, which revealed the partial mediating role of lower extremity muscle strength in this relationship.

Visible-Light-Driven Multicomponent Cyclization by Trapping a 1,3-Vinylimine Ion Intermediate: A Direct Approach to Pyrimido[1,2-b]indazole Derivatives.

Here we develop a novel visible-light-driven three-component cyclization by trapping an 1,3-vinylimine ion intermediate for the direct synthesis of pyrimido[1,2-b]indazole derivatives from bromodifluoroacetic acid derivatives, enaminones, and 3-aminoindazoles under mild conditions. Notably, the robust methodology provides a valuable opportunity for the introduction of aliphatic substituents and enables good compatibility of complex bioactive molecules. Furthermore, this is the first example of photoinduced multicomponent reaction by employing bromodifluoroacetic acid derivatives as a C1-synthon.

The Difficulties and Mental Health Intervention Need of Doctors and Nurses in Biological Emergencies: A Qualitative Study.

When a biological public health event breaks out, due to the characteristics of their work, doctors and nurses must face risks directly when the situation is unknown. Their difficulties and psychological pressure are unimaginable. However, few studies have investigated the difficulties encountered by those doctors and nurses and their requirements for psychological interventions. This study aimed to explore the difficulties and psychological intervention needs of doctors and nurses during the new biological public health events in China in 2019. We carried out a qualitative study using a phenomenological approach. We used convenience sampling to identify participants who provided direct care and treatment for patients with biological events such as coronavirus disease 2019 (COVID-19). They participated in semi-structured, in-depth face-to-face interviews. The interviews were transcribed and analyzed using Colaizzi's seven-step method. Analysis of this study was divided into the difficulties encountered by doctors and nurses and their mental health need. The difficulties encountered by doctors and nurses included four themes: being worried about the impact on others, lack of knowledge and skills, difficult patients, being socially isolated, and the feeling of uncertainty. The mental health need was summarized into two parts, needs expressed by doctors and nurses and needs observed by researchers. Doctors and nurses mostly did not feel that they needed any psychological support, but the researchers noticed several signs of stress or potential mental health problems among interviewees. Doctors and nurses faced significant complex and multidimensional difficulties. Many denied needing psychological support, even though the researchers noted signs that it might be helpful. Interventions and support strategies that involve mental health promotion activities should consider individual needs related to doctors and nurses' situation.

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

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

Impact of diabetes on the risk of bedsore in patients undergoing surgery: an updated quantitative analysis of cohort studies.

Diabetes is a major cause of morbidity for patients undergoing surgery and can increase the incidence of some postoperative complications such as bedsores. We conducted a meta-analysis of observational studies to examine whether patients with diabetes undergoing surgery had high risk of bedsore. We performed a systematic literature search in Pubmed, Embase and the Cochrane Library Central Register of Controlled Trials database from inception to November 2016. Studies were selected if they reported estimates of the relative risk (RR) for bedsore risk in postoperative diabetic patients compared with that of in non-diabetic patients. Random-effects meta-analysis was conducted to pool the estimates. A total of 16 studies with 24,112 individuals were included in our meta-analysis. The pooled RR of bedsore development for patients with diatetes was 1.77 (95% CI 1.45 to 2.16). The results of subgroup analyses were consistent when stratified by surgery type, study design, research region, sample size, inclusion period, analysis method and study quality. There was evidence of publication bias among studies and a sensitivity analysis using the Duval and Tweedie "trim-and-fill" method did not significantly alter the pooled results (adjusted RR 1.17, 95% CI 1.02 to 1.36).This meta-analysis provides indications that diabetic patients undergoing surgery could have a higher risk of developing bedsores. Further large-scale prospective trials should be implemented to comfirm the association.

Acupuncture treatment on the motor area of the scalp for motor dysfunction in patients with ischemic stroke: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture has shown a remarkable treatment efficacy on motor dysfunction in patients with stroke in China, especially the motor area of Jiao's scalp acupuncture, which is the most widely used treatment. However, previous studies have summarized that the clinical curative effect of acupuncture treatment for stroke remains uncertain. Meanwhile, no randomized controlled trials on Jiao's scalp acupuncture have been performed. The aim of this study is to evaluate the efficacy and safety of Jiao's scalp acupuncture for motor dysfunction in ischemic stroke. METHODS/DESIGN: This is an assessor- and analyst-blinded, randomized controlled trial. One hundred and eight stroke patients with motor dysfunction meeting the inclusion criteria will be allocated by a 1:1 ratio into either an acupuncture treatment group or a control group. Stroke patients in the control group will receive conventional rehabilitation treatment, whereas a combination of Jiao's scalp acupuncture and conventional rehabilitation treatment will be applied to the acupuncture group. Forty treatment sessions will be performed over an 8-week period. The Fugl-Meyer Assessment scale will be assessed as the primary outcome measure. The Modified Barthel Index, the Stroke-Specific Quality of Life, and the Stroke Syndrome of Traditional Chinese Medicine scales will be selected as secondary outcome measurements. All assessments will be conducted at baseline, week 4 (treatment 20), week 8 (treatment 40), week 12 (follow-up), and week 16 (follow-up). DISCUSSION: This is the first trial evaluating the efficacy and safety of Jiao's scalp acupuncture for motor dysfunction in ischemic stroke. The results of this trial are expected to provide relevant evidence demonstrating that Jiao's scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in ischemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02871453 . Registered on 17 July 2016.