Sanguinarine Induces Necroptosis of HCC by Targeting PKM2 Mediated Energy Metabolism.

BACKGROUNDS: Abnormal metabolism is the hallmark of hepatocellular carcinoma. Targeting energy metabolism has become the major focus of cancer therapy. The natural product, sanguinarine, displays remarkable anti-tumor properties by disturbing energy homeostasis; however, the underlying mechanism has not yet been elucidated. METHODS: The anticancer activity of sanguinarine was determined using CCK-8 and colony formation assay. Morphological changes of induced cell death were observed under electron microscopy. Necroptosis and apoptosis related markers were detected using western blotting. PKM2 was identified as the target by transcriptome sequencing. Molecular docking assay was used to evaluate the binding affinity of sanguinarine to the PKM2 molecule. Furthermore, Alb-CreERT2; PKM2loxp/loxp; Rosa26RFP mice was used to construct the model of HCC-through the intervention of sanguinarine in vitro and in vivo-to accurately explore the regulation effect of sanguinarine on cancer energy metabolism. RESULTS: Sanguinarine inhibited tumor proliferation, metastasis and induced two modes of cell death. Molecular docking of sanguinarine with PKM2 showed appreciable binding affinity. PKM2 kinase activity and aerobic glycolysis rate declined, and mitochondrial oxidative phosphorylation was inhibited by sanguinarine application; these changes result in energy deficits and lead to necroptosis. Additionally, sanguinarine treatment prevents the translocation of PKM2 into the nucleus and suppresses the interaction of PKM2 with ß-catenin; the transcriptional activity of PKM2/ß-catenin signaling and its downstream genes were decreased. CONCLUSIONS: Sanguinarine showed remarkable anti-HCC activity via regulating energy metabolism by PKM2/ß-catenin signaling. On the basis of these investigations, we propose that sanguinarine might be considered as a promising compound for discovery of anti-HCC drugs.

Efficacy of electrical stimulation for post-stroke motor dysfunction: A protocol for systematic review and network meta-analysis.

OBJECTIVE: This study aims to analyze the efficacy and safety of different electrical stimulation treatments for post-stroke motor dysfunction, and to quantitatively analyze the advantages between them and their possible benefits for patients. METHODS: We will systematically search seven databases. All of them will be retrieved from inception to 15, April 2024. Two reviewers will evaluation the risk of bias in all included studies with the version 2 of the Cochrane risk-of-bias assessment tool. Data synthesis will be performed using a random-effects model of network meta-analysis to compare the efficacy and safety of different electrical stimulation therapies. The surface under the cumulative ranking curve was used to indicate the possibility of the pros and cons of the intervention. The strength of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This study will provide evidence that electrical stimulation therapy can effectively improve motor function in stroke patients and will also provide some valuable references for clinical decision-making and treatment guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42023459102.

Identifying the Local Influencing Factors of Arsenic Concentration in Suburban Soil: A Multiscale Geographically Weighted Regression Approach.

Exploring the local influencing factors and sources of soil arsenic (As) is crucial for reducing As pollution, protecting soil ecology, and ensuring human health. Based on geographically weighted regression (GWR), multiscale GWR (MGWR) considers the different influence ranges of explanatory variables and thus adopts an adaptative bandwidth. It is an effective model in many fields but has not been used in exploring local influencing factors and sources of As. Therefore, using 200 samples collected from the northeastern black soil zone of China, this study examined the effectiveness of MGWR, revealed the spatial non-stationary relationship between As and environmental variables, and determined the local impact factors and pollution sources of As. The results showed that 49% of the samples had arsenic content exceeding the background value, and these samples were mainly distributed in the central and southern parts of the region. MGWR outperformed GWR with the adaptative bandwidth, with a lower Moran's I of residuals and a higher R2 (0.559). The MGWR model revealed the spatially heterogeneous relationship between As and explanatory variables. Specifically, the road density and total nitrogen, clay, and silt contents were the primary or secondary influencing factors at most points. The distance from an industrial enterprise was the secondary influencing factor at only a few points. The main pollution sources of As were thus inferred as traffic and fertilizer, and industrial emissions were also included in the southern region. These findings highlight the importance of considering adaptative bandwidths for independent variables and demonstrate the effectiveness of MGWR in exploring local sources of soil pollutants.

Genetic characterization and molecular epidemiological analysis of enterovirus C99 in China.

Enterovirus C99 (EV-C99) is a newly identified EV serotype within the species Enterovirus C. Few studies on EV-C99 have been conducted globally. More information and research on EV-C99 are needed to assess its genetic characteristics, phylogenetic relationships, and associations with enteroviral diseases. Here, the phylogenetic characteristics of 11 Chinese EV-C99 strains have been reported. The full-length genomic sequences of these 11 strains show 79.4-80.5% nucleotide identity and 91.7-94.3% amino acid (aa) identity with the prototype EV-C99. A maximum likelihood phylogenetic tree constructed based on the entire VP1 coding region identified 13 genotypes (A-M), revealing a high degree of variation among the EV-C99 strains. Phylogeographic analysis showed that the Xinjiang Uygur Autonomous Region is an important source of EV-C99 epidemics in various regions of China. Recombination analysis revealed inter-serotype recombination events of 16 Chinese EV-C99 strains in 5' untranslated regions and 3D regions, resulting in the formation of a single recombination form. Additionally, the Chinese strain of genotype J showed rich aa diversity in the P1 region, indicating that the genotype J of EV-C99 is still going through variable dynamic changes. This study contributes to the global understanding of the EV-C99 genome sequence and holds substantial implications for the surveillance of EV-C99.

Sample size estimation in acupuncture imaging research. / æ ·æœ¬é‡ä¼°ç®—åœ¨é’ˆç¸å½±åƒå­¦ç ”ç©¶ä¸­çš„åº”ç”¨ä¸Žæ€è€ƒ.

The size of the sample significantly impacts the accuracy of research outcomes. While preliminary results have been achieved in acupuncture imaging research, sample size estimation is often subjective and arbitrary, leading to insufficient reliability of study results. This article reviews the current application of sample size estimation in acupuncture imaging research, and provides recommendations to address existing issues. It is suggested that future researches should include the sample sizes that meet statistical power based on the characteristics of functional magnetic resonance imaging (fMRI) protocols, with group sizes of 12 and 20-30 cases having become the "minimum requirement" for confirmatory studies and a common choice. Additionally, the adoption of adaptive design approaches, which dynamically adjust sample sizes based on accumulated data, can be considered. Furthermore, efforts should be made to establish an open platform for sharing acupuncture imaging data to enhance data accessibility, and consequently, improve the quality and overall impact of acupuncture imaging research.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Molecular Epidemiology and Evolution of Coxsackievirus A14.

As the proportion of non-enterovirus 71 and non-coxsackievirus A16 which proportion of composition in the hand, foot, and mouth pathogenic spectrum gradually increases worldwide, the attention paid to other enteroviruses has increased. As a member of the species enterovirus A, coxsackievirus A14 (CVA14) has been epidemic around the world until now since it has been isolated. However, studies on CVA14 are poor and the effective population size, evolutionary dynamics, and recombination patterns of CVA14 are not well understood. In this study, 15 CVA14 strains were isolated from HFMD patients in mainland China from 2009 to 2019, and the complete sequences of CVA14 in GenBank as research objects were analyzed. CVA14 was divided into seven genotypes A-G based on an average nucleotide difference of the full-length VP1 coding region of more than 15%. Compared with the CVA14 prototype strain, the 15 CVA14 strains showed 84.0-84.7% nucleotide identity in the complete genome and 96.9-97.6% amino acid identity in the encoding region. Phylodynamic analysis based on 15 CVA14 strains and 22 full-length VP1 sequences in GenBank showed a mean substitution rate of 5.35 × 10-3 substitutions/site/year (95% HPD: 4.03-6.89 × 10-3) and the most recent common ancestor (tMRCA) of CVA14 dates back to 1942 (95% HPD: 1930-1950). The Bayesian skyline showed that the effective population size had experienced a decrease-increase-decrease fluctuation since 2004. The phylogeographic analysis indicated two and three possible migration paths in the world and mainland China, respectively. Four recombination patterns with others of species enterovirus A were observed in 15 CVA14 strains, among which coxsackievirus A2 (CVA2), coxsackievirus A4 (CVA4), coxsackievirus A6 (CVA6), coxsackievirus A8 (CVA8), and coxsackievirus A12 (CVA12) may act as recombinant donors in multiple regions. This study has filled the gap in the molecular epidemiological characteristics of CVA14, enriched the global CVA14 sequence database, and laid the epidemiological foundation for the future study of CVA14 worldwide.

Clinical study of low-frequency acupoint electrical stimulation to improve thumb-to-finger movements after stroke: A randomized controlled trial.

OBJECTIVE: To examine the effect of low-frequency acupoint electrical stimulation (LFES) on the surface electromyographic (sEMG) signals of the thumb-to-finger movement muscles in stroke patients, and to evaluate the clinical efficacy of LFES on hand function recovery after stroke. METHODS: Sixty patients who met the inclusion criteria were randomly assigned to a LFES group or an electroacupuncture (EA) group, with 30 patients in each group. Both groups received conventional treatment, and the EA group was treated with acupoints from the book of Acupuncture and Moxibustion, while the LFES group was treated with acupoints from a previous study. The sEMG characteristic values (maximum value and RMS), Chinese Stroke Clinical Neurological Deficit Scale (CSS), Brunnstrom Motor Function Evaluation, Modified Ashworth Scale (MAS), Lindmark Hand Function Score and Lovett Muscle Strength Classification were measured before and after treatment. RESULTS: After treatment, both groups showed improvement in sEMG characteristic values, Brunnstrom motor function score, Lindmark hand function score, and Lovett muscle strength classification compared with before treatment, and the improvement in the LFES group was significantly better than that in the EA group (P < .05). The CSS score and MAS classification of both groups decreased compared with before treatment, and the decrease in the LFES group was significantly better than that in the EA group (P < .05). The total effective rate of the LFES group was 92.86%, and that of the EA group was 79.31%. The difference between the 2 groups was statistically significant (P < .05). CONCLUSION: Both LFES and EA were effective in restoring thumb-to-finger movement function after stroke, as evidenced by the increased maximum value and root mean square values of the first dorsal interosseous muscle and the extensor pollicis brevis muscle, the decreased CSS score, the increased Brunnstrom motor function score, the decreased MAS classification, the increased Lindmark hand function score, and the increased Lovett muscle strength classification. However, LFES showed more obvious improvement and better efficacy than EA, which is worthy of clinical promotion.

The efficacy of acupuncture combined with other therapies in post stroke cognitive impairment: A network meta-analysis.

BACKGROUND: The network meta-analysis was used to evaluate the efficacy of acupuncture combined with other therapies in the treatment of post stroke cognitive impairment (PSCI). METHODS: The China National Knowledge Infrastructure, Wanfang DATA, Vip Chinese Periodic Service Platform, PUBMED, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trials (RCTs) published before March 18, 2023. Two researchers independently reviewed articles and extracted data, and then qualified papers were included in the study. STATA 14.0 was used for network meta-analysis. RESULTS: A total of 29 articles including 2241 patients were included in this study. The treatment of the intervention group includes acupuncture combined with traditional Chinese medicine prescriptions (TCMP), acupuncture combined with hyperbaric oxygen (HBO), acupuncture combined with repetitive transcranial magnetic stimulation (rTMS), acupuncture combined with cognitive rehabilitation (CR), acupuncture combined with donepezil. The intervention of the control group includes acupuncture, HBO, rTMS, CR, TCMP, and donepezil. In terms of improving the score of Minimum Mental State Examination (MMSE), acupuncture combined with TCMP was most likely to be the best treatment (P < .05). In terms of improving the score of Montreal Cognitive Assessment (MoCA), acupuncture combined with TCMP was most likely to be the best treatment (P < .05). In terms of improving the total effective rate of clinical treatment, acupuncture combined with rTMS was most likely to be the best treatment (P < .05). CONCLUSION: Acupuncture combined with TCMP may be the best treatment method among all of the above treatments for PSCI.

Genetic characterization and molecular evolution of type 3 vaccine-derived polioviruses from an immunodeficient patient in China.

In 2013, a case of immunodeficiency vaccine-derived poliovirus (iVDPV) was identified in Jiangxi Province, China. In this study, we purified 14 type 3 original viral isolates from this case and characterized the molecular evolution of these iVDPVs for 298 days. Genetic variants were found in most of the original viral isolates, with complex genetic and evolutionary relationships among the variants. A phylogenetic tree constructed based on the P1 region showed that these iVDPVs were classified into lineage A and B. The dominant lineage B represents a major trend in virus evolution. The nucleotide substitution rate at the third codon position (3CP) estimated by the BEAST program was 1.76 × 10-2 substitutions/site/year (95% HPD: 1.23-2.39 × 10-2). The initial OPV dose was given dating back to March 2013, which was close to the time of the last OPV vaccination, suggesting that OPV infection may have originated with the last dose of vaccine. Recombinant analysis showed that these iVDPVs were inter-vaccine recombinants with two recombination patterns, S3/S2/S1 and S3/S2/S3/S2/S1. Whole genome sequence analysis revealed that key nucleotide sites (C472U, C2034U, U2493C) associated with the attenuated phenotype of Sabin 3 have been replaced. Temperature sensitivity test showed that all tested strains were temperature-sensitive, except for the variant Day11-5. Interestingly, we observed that the variant Day11-5 temperature resistance properties may be associated with the Lys to Met substitution at the VP2-162 site. Serological test and whole genome sequence analysis showed that the seropositivity rate remained high, and mutations in the antigenic sites did not significantly alter neutralization ability.

Effects of electroacupuncture therapy on intractable facial paralysis: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assessment effects of electroacupuncture (EA) therapy on intractable facial paralysis. METHODS: The articles of EA treatment for intractable facial paralysis were retrieved from seven databases, the publication period was from its inception to November 30, 2022. Primary measure was the total effective rate, and other measures included the cure rate, Portmann scores, House-Brackmann scores, Sunnybrook scores and adverse events. The effect size of meta-analysis was expressed using relative risk (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: A total of 18 studies with 1,119 participants were included, all of them had various aspects of bias risk. Meta-analysis results revealed that EA ways improved total effective rate more effectively compared with non-EA counterparts (RR 1.23, 95% CI 1.17-1.31, I2 = 0%, 18 studies, 1119 participants), and improved cure rate more significantly than non-EA groups (RR 2.04, 95% CI 1.70-2.44, I2 = 0%, 18 studies, 1119 participants). None of studies reported adverse events. CONCLUSION: EA therapy is more beneficial for patients with intractable facial paralysis than non-EA, but we lack sufficient evidence to evaluate its safety and follow-up effect. Therefore, more clinical trials with high quality methodologies are needed to further verify long-term effects of EA for IFP and improve the level of evidence. TRIAL REGISTRATION: Registration number: CRD42021278541.

Treatment of Parkinson disease by acupuncture combined with medicine based on syndrome differentiation from the perspective of modern medicine: A review.

As a multifactorial degenerative disease, Parkinson disease (PD) causes tremor, gait rigidity, and hypokinesia, which interfere with normal life. Because the disease is usually discovered in the late stage of complete degeneration of neurons, it can greatly delay treatment and even eventually lead to death. Therefore, the diagnosis of this disease is very challenging, and it is gratifying that substantial progress has been made in the development of optical coherence tomography (OCT) as a diagnostic biomarker for this disease, and genetic and imaging tests have become part of routine protocols in clinical practice. In the cognition of traditional Chinese medicine (TCM), this disease belongs to deficiency in origin and excess in superficiality, which is always caused by deficiency of liver and kidney, deficiency of qi and blood, and is closely related to wind, fire, phlegm and blood stasis. A large number of studies have shown that TCM can effectively treat motor and non-motor symptoms of PD, combat oxidative stress and reduce inflammatory response, and improve the quality of life of patients. Based on the pathophysiological mechanism of PD, this paper discusses the treatment of PD by TCM acupuncture combined with medicine based on syndrome differentiation.

MSCs Deliver Hypoxia-Treated Mitochondria Reprogramming Acinar Metabolism to Alleviate Severe Acute Pancreatitis Injury.

Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member of stem cells with immunomodulatory and anti-inflammatory capabilities that can mitigate damage in experimental pancreatitis. Here, it is shown that MSCs deliver hypoxia-treated functional mitochondria to damaged pancreatic acinar cells (PACs) via extracellular vesicles (EVs), which reverse the metabolic function of PACs, maintain ATP supply, and exhibit an excellent injury-inhibiting effect. Mechanistically, hypoxia inhibits superoxide accumulation in the mitochondria of MSCs and upregulates the membrane potential, which is internalized into PACs via EVs, thus, remodeling the metabolic state. In addition, cargocytes constructed via stem cell denucleation as mitochondrial vectors are shown to exert similar therapeutic effects to MSCs. These findings reveal an important mechanism underlying the role of mitochondria in MSC therapy and offer the possibility of applying mitochondrial therapy to patients with severe acute pancreatitis.

18F-FDG PET-CT for the prediction of mortality in patients with dermatomyositis and without malignant tumors: a pilot study.

Background: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) is typically used to screen malignancy in patients with dermatomyositis (DM). The aim of this study was to investigate the value of using PET-CT in assessing the prognosis of patients with DM and without malignant tumors. Methods: A total of 62 patients with DM who underwent 18F-FDG PET-CT were enrolled in the retrospective cohort study. Clinical data and laboratory indicators were obtained. The muscle max standardized uptake value (SUVmax), splenic SUVmax, target-to-background ratio (TBR) of the aorta, pulmonary highest value (hv)/SUVmax, epicardial fat volume (EFV), and coronary artery calcium (CAC) were measured using 18F-FDG PET-CT. The follow-up was conducted until March 2021, and the endpoint was death from any cause. Univariable and multivariable Cox regression analyses were used to analyze prognostic factors. The survival curves were produced with the Kaplan-Meier method. Results: The median duration of follow-up was 36 [interquartile range (IQR), 14-53] months. The survival rates were 85.2% and 73.4% for 1 and 5 years, respectively. A total of 13 (21.0%) patients died during a median follow-up of 7 (IQR, 4-15.5) months. Compared with the survival group, the death group had significantly higher levels of C-reactive protein [CRP; median (IQR), 4.2 (3.0, 6.0) vs. 6.30 (3.7, 22.8)], hypertension [7 (14.3%) vs. 6 (46.2%)], interstitial lung disease [ILD; 26 (53.1%) vs. 12 (92.3%)], positive anti-Ro52 antibody [19 (38.8%) vs. 10 (76.9%)], pulmonary FDG uptake [median (IQR), 1.8 (1.5, 2.9) vs. 3.5 (2.0, 5.8)], CAC [1 (2.0%) vs. 4 (30.8%)], and EFV [median (IQR), 74.1 (44.8, 92.1) vs. 106.5 (75.0, 128.5)] (all P values <0.001). Univariable and multivariable Cox analyses identified high pulmonary FDG uptake [hazard ratio (HR), 7.59; 95% confidence interval (CI), 2.08-27.76; P=0.002] and high EFV (HR, 5.86; 95% CI, 1.77-19.42; P=0.004) as independent risk factors for mortality. The survival rate was significantly lower in patients with the concurrent presence of high pulmonary FDG uptake and high EFV. Conclusions: Pulmonary FDG uptake and EFV detected with PET-CT were independent risk factors for death in patients with DM and without malignant tumors. Patients with the concurrent presence of high pulmonary FDG uptake and high EFV had a worse prognosis compared with patients with 1 or neither of these two risk factors. Early treatment should be applied in patients with concurrent presence of high pulmonary FDG uptake and high EFV to improve the survival rate.

Differences and Clinical Significance of Serum 25-Hydroxyvitamin D3 and Vasohibin-1 (VASH-1) Levels in Patients with Diabetic Nephropathy and Different Renal Injuries.

Objective: We investigate the relationship between the changes of serum 25-hydroxyvitamin D3 (25(OH)D3) and vasohibin-1 (VASH-1) and renal function injury in patients with type 2 diabetic nephropathy. Methods: In this study, 143 patients with diabetic nephropathy (DN) were selected as DN group, and 80 patients with type 2 diabetes mellitus were selected as T2DM group. The serum 25 (OH) D3, VASH-1, blood glucose index, inflammation index and renal function index were compared between the two groups. According to the urinary microalbumin/creatinine ratio (UACR), the DN group was divided into microalbuminuria group (UACR range≥30.0mg/g and <300.0mg/g) and macroalbuminuria group (UACR≥300.0mg/g) for stratified comparison. The correlation between 25-hydroxyvitamin D3, VASH-1 and inflammation index and renal function index was analyzed by simple linear correlation analysis. Results: The level of 25 (OH) D3 in DN group was significantly lower than that in T2DM group (P<0.05). The levels of VASH-1, CysC, BUN, Scr, 24h urine protein, serum CRP, TGF-ß1, TNF-α and IL-6 in DN group were higher than those in T2DM group (P<0.05). The level of 25 (OH) D3 in DN patients with massive proteinuria was significantly lower than that in DN patients with microalbuminuria. The level of VASH-1 in DN patients with massive proteinuria was higher than that in DN patients with microalbuminuria (P<0.05). There was a negative correlation between 25 (OH) D3 and CysC, BUN, Scr, 24h urine protein, CRP, TGF-ß1, TNF-α, IL-6 in patients with DN (P<0.05). VASH-1 was positively correlated with Scr, 24h urinary protein, CRP, TGF-ß1, TNF-α and IL-6 in patients with DN (P<0.05). Conclusion: The level of serum 25 (OH) D3 in DN patients was considerably decreased, and the level of VASH-1 was increased, which was related to the degree of renal function injury and inflammatory response.

Effects of programmed flexor-extensor alternating electrical acupoint stimulation on upper limb motor functional reconstruction after stroke: study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Stroke's prevalence and morbidity are increasing (Guano, et al. Neuro 89:53-61, 2017), and limb motor dysfunction is left in most patients (Gittler, et al. JAMA 319:820-821, 2018). Particularly, the rehabilitation of upper limbs is more difficult and time-consuming (Borges, et al. The Cochrane database of systematic reviews 10:CD011887, 2018). METHODS: A double-blind randomized controlled trial (RCT) will be conducted to investigate whether a new functional electrical stimulation (FES) combined with acupoint therapy is more effective in the rehabilitation of upper limb motor dysfunction after stroke. Patients who meet the inclusion criteria will be randomly divided into two groups: programmed flexor-extensor alternating electrical acupoint stimulation group (PES group) and conventional flexor-extensor alternating electrical acupoint stimulation group (CES group), which will be treated for 3 weeks. The primary outcome measures are electroencephalogram (EEG) and surface electromyogram (sEMG). The secondary outcome variables include MBI (modified Barthel index), China Stroke Scale (CSS), FMA-U (Fugl-Meyer assessment upper limb), MMT (manual muscle testing), and Brunnstrom. DISCUSSION: The results of this study are expected to verify the efficacy of PES therapy in the rehabilitation of upper limb motor function after stroke. This may promote the widespread use of the therapy in hospitals, communities, and homes for early and continuous treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05333497. Registered on April 11, 2022.

[Professor SUN Shen-tian's experience in acupuncture treatment of depression based on "psychosomatic medicine"].

This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.

ROS Scavenging and inflammation-directed polydopamine nanoparticles regulate gut immunity and flora therapy in inflammatory bowel disease.

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. STATEMENT OF SIGNIFICANCE: Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis.

Basic Fibroblast Growth Factor Promotes Mesenchymal Stem Cell Migration by Regulating Glycolysis-Dependent ß-Catenin Signaling.

Migration of mesenchymal stem cells (MSCs) to the site of injury is crucial in transplantation therapy. Studies have shown that cell migration is regulated by the cellular microenvironment and accompanied by changes in cellular metabolism. However, limited information is available about the relationship between MSC migration and cellular metabolism. Here, we show that basic fibroblast growth factor (bFGF) promotes the migration of MSCs with high levels of glycolysis and high expression of hexokinase 2 (HK2), a rate-limiting enzyme in glycolysis. The enhancement of glycolysis via the activation of HK2 expression promoted the migration of MSCs, whereas the inhibition of glycolysis, but not of oxidative phosphorylation, inhibited the bFGF-induced migration of these cells. Furthermore, bFGF enhanced glycolysis by increasing HK2 expression, which consequently promoted ß-catenin accumulation, and the inhibition of glycolysis inhibited the bFGF-induced accumulation of ß-catenin. When the accumulation of glycolytic intermediates was altered, phosphoenolpyruvate was found to be directly involved in the regulation of ß-catenin expression and activation, suggesting that bFGF regulates ß-catenin signaling through glycolytic intermediates. Moreover, transplantation with HK2-overexpressing MSCs significantly improved the effect of cell therapy on skull injury in rats. In conclusion, we propose a novel glycolysis-dependent ß-catenin signaling regulatory mechanism and provide an experimental and theoretical basis for the clinical application of MSCs.

Luteoloside Induces G0/G1 Phase Arrest of Neuroblastoma Cells by Targeting p38 MAPK.

Luteoloside has shown anti-inflammatory, antiviral, and antitumor properties. However, the effect and mechanism of luteoloside on neuroblastoma cells remain unknown. The proliferation of human neuroblastoma cells (SH-SY5Y and SK-N-AS) treated with different concentrations of luteoloside (0, 12.5, 25, and 50 µM) was detected by the MTT assay and colony formation assay. Cell apoptosis and cell cycle were examined by Hoechst staining and flow cytometry. A subcutaneous tumorigenesis model was established in nude mice to evaluate the effect of luteoloside on tumor growth in vivo. Bioinformatics, molecular docking techniques, and cellular thermal shift assays were utilized to predict the potential targets of luteoloside in neuroblastoma. The p38 MAPK inhibitor SB203580 was used to confirm the role of p38 MAPK. Luteoloside inhibited the proliferation of neuroblastoma cells in vitro and in vivo. Luteoloside slightly induced cellular G0/G1 phase arrest and reduced the expression levels of G0/G1 phase-related genes and the proteins cyclin D1, CDK4, and C-myc, which are downregulated by p38 MAPK pathways. Meanwhile, p38 was identified as the target of luteoloside, and inhibition of p38 MAPK reversed the inhibitory effect of luteoloside on neuroblastoma cells. Luteoloside is a potential anticancer drug for treating neuroblastoma by activating p38 MAPK.