Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis.

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63-0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541-0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer-Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

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.

Efficacy and safety of ultra-short wave diathermy on COVID-19 pneumonia: a pioneering study.

Background: The ultra-short wave diathermy (USWD) is widely used to ameliorate inflammation of bacterial pneumonia, however, for COVID-19 pneumonia, USWD still needs to be verified. This study aimed to investigate the efficacy and safety of USWD in COVID-19 pneumonia patients. Methods: This was a single-center, evaluator-blinded, randomized controlled trial. Moderate and severe COVID-19 patients were recruited between 18 February and 20 April 2020. Participants were randomly allocated to receive USWD + standard medical treatment (USWD group) or standard medical treatment alone (control group). The negative conversion rate of SARS-CoV-2 and Systemic Inflammatory Response Scale (SIRS) on days 7, 14, 21, and 28 were assessed as primary outcomes. Secondary outcomes included time to clinical recovery, the 7-point ordinal scale, and adverse events. Results: Fifty patients were randomized (USWD, 25; control, 25), which included 22 males (44.0%) and 28 females (56.0%) with a mean (SD) age of 53 ± 10.69. The rates of SARS-CoV-2 negative conversion on day 7 (p = 0.066), day 14 (p = 0.239), day 21 (p = 0.269), and day 28 (p = 0.490) were insignificant. However, systemic inflammation by SIRS was ameliorated with significance on day 7 (p = 0.030), day 14 (p = 0.002), day 21 (p = 0.003), and day 28 (p = 0.011). Time to clinical recovery (USWD 36.84 ± 9.93 vs. control 43.56 ± 12.15, p = 0.037) was significantly shortened with a between-group difference of 6.72 ± 3.14 days. 7-point ordinal scale on days 21 and 28 showed significance (p = 0.002, 0.003), whereas the difference on days 7 and 14 was insignificant (p = 0.524, 0.108). In addition, artificial intelligence-assisted CT analysis showed a greater decrease in the infection volume in the USWD group, without significant between-group differences. No treatment-associated adverse events or worsening of pulmonary fibrosis were observed in either group. Conclusion: Among patients with moderate and severe COVID-19 pneumonia, USWD added to standard medical treatment could ameliorate systemic inflammation and shorten the duration of hospitalization without causing any adverse effects.Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2000029972.

Investigation of therapeutic effects of rhubarb decoction retention enema on minimal hepatic encephalopathy in rats based on 16S rDNA gene sequencing and bile acid metabolomics.

Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE), with high incidence and a high rate of clinically missed diagnosis. Early diagnosis of MHE and effective clinical intervention are of great importance. Rhubarb decoction (RD)-induced retention enema can effectively improve the cognitive function of patients with MHE, whereas disturbances in the enterohepatic circulation of bile acid (BAs) can induce MHE. However, the molecular mechanisms underlying the therapeutic effects of RD have not been examined from the perspective of intestinal microbiota and bile metabolomics. In this study, we investigated the effects of RD-induced retention enema on intestinal microbiota and bile metabolites in rats with CCl4- and TAA-induced MHE. RD-induced retention enema significantly improved liver function, reduced blood ammonia levels, alleviated cerebral oedema and restored cognitive function in rats with MHE. In addition, it increased the abundance of intestinal microbes; partially reversed the disorder in the composition of intestinal microbiota, including the Bifidobacterium and Bacteroides genera; and regulated BA metabolism, such as taurine combined with increased BA synthesis. In conclusion, this study highlights the potential importance of BA enterohepatic circulation for RD to improve cognitive function in MHE rats, providing a new perspective on the mechanism of this herb. The findings of this study will facilitate experimental research on RD and help to develop RD-based strategies for clinical application.

Spinal dI4 Interneuron Differentiation From Human Pluripotent Stem Cells.

Spinal interneurons (INs) form intricate local networks in the spinal cord and regulate not only the ascending and descending nerve transduction but also the central pattern generator function. They are therefore potential therapeutic targets in spinal cord injury and diseases. In this study, we devised a reproducible protocol to differentiate human pluripotent stem cells (hPSCs) from enriched spinal dI4 inhibitory GABAergic INs. The protocol is designed based on developmental principles and optimized by using small molecules to maximize its reproducibility. The protocol comprises induction of neuroepithelia, patterning of neuroepithelia to dorsal spinal progenitors, expansion of the progenitors in suspension, and finally differentiation into mature neurons. In particular, we employed both morphogen activators and inhibitors to restrict or "squeeze" the progenitor fate during the stage of neural patterning. We use retinoic acid (RA) which ventralizes cells up to the mid-dorsal region, with cyclopamine (CYC), an SHH inhibitor, to antagonize the ventralization effect of RA, yielding highly enriched dI4 progenitors (90% Ptf1a+, 90.7% Ascl1+). The ability to generate enriched spinal dI4 GABAergicINs will likely facilitate the study of human spinal IN development and regenerative therapies for traumatic injuries and diseases of the spinal cord.

Generation of an induced pluripotent stem cell line HUSTTJi001-A from a Moyamoya disease patient with RNF213 gene mutation.

Moyamoya disease (MMD) is an idiopathic and chronic steno-occlusive cerebrovascular disease. Genetic studies identified RNF213 as a principal susceptibility gene of MMD. In this study, peripheral blood mononuclear cells (PBMCs) were obtained from an MMD patient with RNF213 p. R4810K mutations, and the PBMCs were then reprogrammed to induced pluripotent stem cells (iPSCs) by the transfection of non-integrated episomal vectors. The iPSC line shows pluripotency markers and has the potential for in vitro differentiation into three germ layers, and will be valuable for elucidating the underlying cellular mechanisms of MMD, selecting therapeutic targets, and developing drugs.

Scaling the Need, Benefits, and Risks Associated with COVID-19 Acute and Postacute Care Rehabilitation: A Review.

Coronavirus is an RNA virus, which attacks the respiratory system causing complications including severe respiratory distress and pneumonia and many other symptoms. Recently, a novel coronavirus (COVID-19) outbreak emerged in Wuhan, which caused a significant number of infections in China and resulted in a global pandemic. The main aim of this study is to review and summarize the evidence regarding the supportive role of physical rehabilitation techniques in managing COVID-19-associated pneumonia. In this review, we also emphasize the use of rehabilitation techniques in the management of pneumonia in COVID-19-infected patients. Based on the evidence presented, we conclude that certain physical rehabilitation techniques and modalities could be of great support in the management of COVID-19-associated pneumonia. The safety of staff and patients when applying rehabilitation intervention requires attention. The combination of physical rehabilitation and medical treatment would result in improved treatment outcomes, faster recovery, and shorter hospital stay. Many rehabilitation techniques are safe and feasible and can be easily incorporated into the management protocol of COVID-19 victims. Decisions of early rehabilitation induction should be based on the patient's medical condition and tolerability.

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.