Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial.

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation.

OBJECTIVE: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge., (Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis (AP) using a network pharmacology approach and validate the findings in animal experiments. METHODS: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation. Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry, Western blot analysis and real-time quantitative PCR, respectively. RESULTS: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3 (MAPK3), Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), protein c-Fos (FOS) were identified as core targets in the protein interaction (PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone II and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1ß, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation (P<0.01). CONCLUSION: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues, which would be functioned by regulating Th17 cell differentiation-related mRNA and protein expressions.

The curative effects of shortwave diathermy on treating Novel coronavirus (COVID-19) pneumonia: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the therapeutic effects of ultra-short-wave diathermy (SWD) on COVID-19 pneumonia. The hypothesis is that SWD may minimise pneumonic inflammation and shorten the duration of the time to positive-to-negative conversion of COVID-19 nucleic acid test. TRIAL DESIGN: This is a single centre, 2-arm (1:1 ratio), evaluator blinded, parallel group design superiority randomised, controlled clinical trial. PARTICIPANTS: The inclusion criteria were: (1) Age 18-65 years, (2) COVID-19 nucleic acid test is positive, (3) Lung CT showed multiple patchy ground glass shadows or other typical manifestations of both lungs. The exclusion criteria were: (1) Patients who need ICU management, (2) Positive tests for other pathogens such as Tuberculosis, Mycoplasma, (3) Patients with respiratory failure or requiring mechanical ventilation, (4) Patients with metal implants or pacemakers, (5) Those with shock (6) Those that have bleeding tendency or active bleeding in the lungs, (7) Patients with multiple organ failure who need ICU monitoring and treatment, (8) Cancer patients and those with severe underlying diseases, (9) Pregnant or lactating women, (10) Patients with severe cognitive impairment who cannot follow the instructions to complete the treatment, (11) Those without signed informed consent and (12) Those with other contraindications to short wave. This study will be conducted in Tongji Hospital, Caidian, Wuhan, People's Republic of China. INTERVENTION AND COMPARATOR: The experimental group will be given the nationally recommended standard medical treatment + ultra-short-wave diathermy treatment. Ultra-short-wave therapy treatment will be performed through application of ultra-short-wave therapy machine electrodes on the anterior and posterior parts of the trunk for 10 minutes, twice a day for 12 consecutive days. The comparator will be the control, not receiving ultra-short-wave therapy, and will be given only the nationally recommended standard medical treatment. MAIN OUTCOMES: The primary outcome measures will be time to positive-to-negative conversion of COVID-19 nucleic acid test by pharyngeal swab, in days assessed at 7th, 14th ,21st and 28th days. The secondary outcome measures include nucleic acid test rate and recovery from symptoms, Vital signs assessment, Computed Tomography, Complete blood count, serum analysis and SIRS scale scores. Blinded evaluation will be at baseline (the day of starting ultra-short-wave diathermy) and after 28 days following the interventions. RANDOMISATION: A Randomization plan will be generated online on www.randomization.com using permuted blocks method, by a statistician who will not be part of the study. Small blocks of various sizes will be used. Patients will be randomized (1:1) between the experimental and control groups BLINDING (MASKING): This will be an evaluator blinded study. Due to the nature of the intervention, blinding of patients and healthcare workers is not possible. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 410 patients will be randomised in 1:1 ratio to two groups: experimental group (n=205) and control group (n=205). TRIAL STATUS: Protocol version 1 was approved on 02/12/2020. Recruitment for this trial began on 02/18/2020 and will be ongoing till the required sample size is reached. The analysis deadline is August 2020. TRIAL REGISTRATION: This randomised controlled trial has been prospectively registered with the Chinese Clinical Trials ( ChiCTR2000029972 ) on 17 February 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol." The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

A Comprehensive Meta-Analysis for Bypass Surgery in Adult Moyamoya.

OBJECTIVE: To evaluate the outcomes of bypass surgery for adult moyamoya and compare different surgical modalities by performing a comprehensive meta-analysis of relevant studies. METHODS: A systematic literature search was performed and articles regarding different treatments for adult patients with moyamoya were included. Odds ratios (ORs) were calculated to evaluate stroke recurrence, mortality, perioperative complications, and angiographic revascularization among different surgical methods and conservative treatment (CT). RESULTS: A total of 17 studies with 2224 adult patients with moyamoya were included in the meta-analysis. Compared with CT, surgical revascularization significantly decreased the future stroke events in the total population ([OR] 0.404; 95% confidence interval [CI] 0.279-0.585; P < 0.001) and in the hemorrhagic-onset patients as well (OR 0.259; 95% CI 0.138-0.486; P < 0.001). However, for those patients with moyamoya and ischemia, there was no significant difference for future stroke events between the bypass and CT groups (OR 0.470; 95% CI 0.140-1.579; P = 0.222). Bypass also showed no mortality reduction compared with CT (OR 0.372; 95% CI 0.120-1.154; P = 0.087). For different surgical techniques, no differences for future stroke events, mortality, and perioperative complications were found between direct bypass and indirect bypass, whereas the degree of angiographic revascularization was better in the direct bypass group than in the indirect group (OR 4.720; 95% CI 1.222-18.230; P = 0.024). CONCLUSIONS: The bypass treatment was superior to conservative treatment in preventing recurrent stroke in adult patients with moyamoya, especially in those with a hemorrhagic onset. Direct bypass is associated with better revascularization results compared with indirect bypass.

Effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery: A meta-analysis.

Cognitive impairments are observed in numerous patients following coronary bypass surgery, and piracetam are nootropic compounds that modulate cerebral functions by directly enhancing cognitive processes. The present meta-analysis was conducted to evaluate the protective effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery. The relevant studies were identified by searching Medline, EMBASE, PubMed and the Cochrane Library up to June 2013 and the pertinent bibliographies from the retrieved studies were reviewed. Data were selected from the studies according to predefined criteria. The meta-analysis included two randomized control trials involving 184 patients and including the Syndrom-Kurz test (SKT). Findings of the meta-analysis showed that following treatment the change from baseline observed in five SKT subtest scores, conducted with piracetam patients, indicated a significant advantage over those patients that were in the placebo group. The subtests included immediate pictured object recall, weighted mean difference (WMD)=0.91, 95% confidence interval (CI) 0.51-1.31, P<0.00001; delayed pictured object recall, WMD=0.74, 95% CI 0.19-1.28, P=0.008; delayed picture recognition, WMD=0.82, 95% CI 0.31-1.31, P=0.001; immediate word recall, WMD=0.87, 95% CI 0.47-1.28, P<0.0001; and letter interference, WMD=3.46, 95% CI -5.69 to -1.23, P=0.002. These results indicated that piracetam may have been effective in improving the short-term cognitive performance of patients undergoing coronary bypass surgery. High quality, well-controlled and longer randomized trials are required to corroborate this result.