Regulatory mechanisms and therapeutic strategies for pyroptosis after spinal cord injury / 中国组织工程研究

BACKGROUND:Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury.Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy. OBJECTIVE:To summarize the molecular mechanism,positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury. METHODS:The search terms were"spinal cord injury,pyroptosis,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase,Gasdermin D(GSDMD),IL-1β,IL-18"and 93 English literatures included in PubMed and Web of Science were finally selected for review. RESULTS AND CONCLUSION:As a newly discovered programmed cell death,pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury.Among the regulatory factors of pyroptosis after spinal cord injury,CD73,NRF2,GDF-11,dopamine,FANCC and miR-423-5P could inhibit pyroptosis,while TLR4 and Aopps could promote pyroptosis.In terms of treatment,the active ingredients of traditional Chinese medicine(paeonol,tripterine,betulinic acid,piperine,kaempferol,and camptothecin),exosomes of various cell origins,and some drugs(metformin,topotecan,lithium,zinc,and carbon monoxide-releasing molecule 3)can effectively inhibit pyroptosis and reduce secondary spinal cord injury,but the toxicity and specific dose of these drugs need to be further studied.The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood.The role of non-classical pathways and other inflammasomes is worth further exploration.At present,the research on pyroptosis after spinal cord injury only stays at the animal experiment stage.There are no related clinical studies and no approved targeted therapeutic drugs.(6)The application of pyroptosis after spinal cord injury has great potential,and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury.

Platelet aggregation rate predicts early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of platelet aggregation rate for early neurological deterioration (END) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS received IVT at the Department of Neurology, Haikou Hospital Affiliated to Xiangya School of Medical, Central South University from November 2020 to July 2023 were retrospectively included. The maximum platelet aggregation rate (MAR) was measured using the PL-12 multi-parameter platelet function analyzer. END was defined as an increase of ≥4 from baseline in the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after IVT. The demographic, baseline data, laboratory findings, and imaging results between the END and non-END groups were compared, and the dynamic changes in MAR induced by arachidonic acid (AA) and adenosine diphosphate (ADP) before, immediately after, and 2 h after IVT were observed. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of MAR for END at different time points. Results:A total of 300 patients were included, aged 64.88±8.82 years, with a median baseline NIHSS score of 11 (interquartile range, 8-15) and the onset-to-needle time was 172.03±53.96 min. Among them, 66 patients (22.0%) developed END. The MAR-AA and MAR-DP levels before, immediately after, and 2 h after IVT in the END group were significantly higher than those in the non-END group (all P<0.05). Multivariate logistic regression analysis showed that MAR-AA (odds ratio 1.098, 95% confidence interval 1.039-1.161; P<0.001) and MAR-ADP (odds ratio 1.100, 95% confidence interval 1.038-1.167; P<0.001) at 2 h after IVT were the independent risk factors for END. ROC curve analysis shows that MAR-AA and MAR-ADP before, immediately after, and 2 h after IVT had good predictive value for END. Among them, the area under the curve corresponding to MAR-AA and MAR-ADP at 2 h after IVT was the largest, with values of 0.745 and 0.710, respectively. The optimal cutoff value of MAR-AA was 39.28%, and the sensitivity and specificity for predicting END were 74.2% and 76.1%, respectively. The optimal cutoff value of MAR-ADP was 43.35%, and the sensitivity and specificity for predicting END were 69.7% and 66.2%, respectively. Conclusion:The MAR measured by PL-12 is closely associated with the risk of END in patients with AIS after IVT treatment, and has good predictive value for END.

The SARS-CoV-2 host cell membrane fusion protein TMPRSS2 is a tumor suppressor and its downregulation correlates with increased antitumor immunity and immunotherapy response in lung adenocarcinoma

BackgroundTMPRSS2 is a host cell membrane fusion protein for SARS-CoV-2 invading human host cells. It also has an association with cancer, particularly prostate cancer. However, its association with lung cancer remains insufficiently explored. Thus, an in-depth investigation into the association between TMPRSS2 and lung cancer is significant, considering that lung cancer is the leading cause of cancer death and that the lungs are the primary organ SARS-CoV-2 attacks. MethodsUsing five lung adenocarcinoma (LUAD) genomics datasets, we explored associations between TMPRSS2 expression and immune signatures, cancer-associated pathways, tumor progression phenotypes, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we validated the findings from the bioinformatics analysis by performing in vitro experiments with the human LUAD cell line A549 and in vivo experiments with mouse tumor models. We also validated our findings in LUAD patients from Jiangsu Cancer Hospital, China. ResultsTMPRSS2 expression levels were negatively correlated with the enrichment levels of CD8+ T and NK cells and immune cytolytic activity in LUAD, which represent antitumor immune signatures. Meanwhile, TMPRSS2 expression levels were negatively correlated with the enrichment levels of CD4+ regulatory T cells and myeloid-derived suppressor cells and PD-L1 expression levels in LUAD, which represent antitumor immunosuppressive signatures. However, TMPRSS2 expression levels showed a significant positive correlation with the ratios of immune-stimulatory/immune-inhibitory signatures (CD8+ T cells/PD-L1) in LUAD. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory signatures than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with elevated activities of many oncogenic pathways in LUAD, including cell cycle, mismatch repair, p53, and extracellular matrix (ECM) signaling. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor advancement, and worse survival in LUAD. In vitro and in vivo experiments validated the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. ConclusionsTMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a connection between lung cancer and pneumonia caused by SARS-CoV-2 infection.

Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach

The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.

Predicting the epidemic trend of COVID-19 in China and across the world using the machine learning approach

BackgroundAlthough COVID-19 has been well controlled in China, it is rapidly spreading outside the country and may have catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most have used early-stage data and focused on Chinese cases. MethodsWe first built models to predict daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on data from January 20, 2020, to March 1, 2020. Based on these models, we built models to predict the epidemic trend across the world (outside China). We also built models to predict the epidemic trend in Italy, Spain, Germany, France, UK, and USA where COVID-19 is rapidly spreading. ResultsThe COVID-19 outbreak will have peaked on February 22, 2020, in China and will peak on May 22, 2020, across the world. It will be basically under control in early April 2020 in China and late August 2020 across the world. The total number of COVID-19 cases will reach around 89,000 in China and 6,126,000 across the world during the epidemic. Around 4,000 and 290,000 people will die of COVID-19 in China and across the world, respectively. The COVID-19 outbreak will have peaked recently in Italy and will peak in Spain, Germany, France, UK, and USA within two weeks. ConclusionThe COVID-19 outbreak is controllable in the foreseeable future if comprehensive and stringent control measures are taken.

Platelet reactivity predicts early neurological deterioration in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the predictive value of platelet reactivity for early neurological deterioration (END) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke within 48 h of onset admitted to the Department of Neurology, the Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University from January 2017 to March 2019 were enrolled prospectively. Aspirin was taken on the day of admission, and the platelet aggregation rate was detected using a PL-11 Platelet Function Analyzer 7 d after taking it. END was defined as the National Institutes of Health Stroke Scale (NHISS) score at any time point within 7 d after admission increased by ≥2 or the motor function item score increased by ≥1 from baseline. The demographics, baseline data, imaging examination and laboratory findings of patients in the END and non-END groups were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of platelet aggregation rate for END. Results:A total of 230 patients were included in the study. They aged 63.24±9.75 years, 126 were females (51.4%). The median baseline NIHSS score was 6 (interquartile range, 4-10). The median time from onset to admission was 15 h (interquartile range, 9-28 h). There were 54 patients (23.5%) in the END group and 176 (76.5%) in the non-END group. There were significant differences in arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA), epinephrine-induced maximum platelet aggregation ratio (MAR-EPI) and collagen-induced maximum platelet aggregation ratio (MAR-COL) between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that MAR-AA (odd ratio [ OR] 1.165, 95% confidence interval [ CI] 1.091-1.243; P<0.001) and MAR-EPI ( OR 1.035, 95% CI 1.006-1.067; P=0.023) were the independent risk factors for END in patients with acute ischemic stroke. ROC curve analysis showed that MAR-AA had good predictive value for END, and the area under the curve was 0.775 (95% CI 0.707-0.843; P<0.001). The optimal cut-off value was 21.80%. The sensitivity and specificity of MAR-AA for predicting END were 72.2% and 77.3%, respectively. Conclusions:The platelet function measured by PL-11 is closely related to the risk of END in patients with acute ischemic stroke. It has a better predictive value for END.

DNA barcoding for identification of fish species in the Taiwan Strait.

DNA barcoding based on a fragment of the cytochrome c oxidase subunit I (COI) gene in the mitochondrial genome is widely applied in species identification and biodiversity studies. The aim of this study was to establish a comprehensive barcoding reference database of fishes in the Taiwan Strait and evaluate the applicability of using the COI gene for the identification of fish at the species level. A total of 284 mitochondrial COI barcode sequences were obtained from 85 genera, 38 families and 12 orders of fishes. The mean length of the sequences was 655 base pairs. The average Kimura two parameter (K2P) distances within species, genera, families, orders and classes were 0.21%, 6.50%, 23.70% and 25.60%, respectively. The mean interspecific distance was 31-fold higher than the mean intraspecific distance. The K2P neighbor-joining trees based on the sequence generally clustered species in accordance with their taxonomic classifications. High efficiency of species identification was demonstrated in the present study by DNA barcoding, and we conclude that COI sequencing can be used to identify fish species.

Clinical efficacy of dexamethasone combined with budesonide in the treatment of children with acute infectious laryngitis / 中国基层医药

Objective@#To investigate the clinical efficacy of dexamethasone combined with budesonide in the treatment of children with acute infectious laryngitis.@*Methods@#From May 2014 to May 2017, 85 children with acute infectious laryngitis in our hospital were randomly divided into observation group(43 cases) and control group(42 cases) according to the digital table.The control group was treated with dexamethasone, the observation group inhaled budesonide on the basis of the dexamethasone treatment.The clinical effect was compared between the two groups.@*Results@#The effective rate of the observation group was significantly higher than that of the control group(97.9% vs.85.7%), the difference was statistically significant(χ2=4.022, P<0.05). The symptoms disappeared time of laryngeal obstruction [(1.2±0.2)d vs.(1.8±0.4)d], hoarseness [(2.2±0.6)d vs.(2.7±0.9)d], dyspnea [(1.5±0.4)d vs.(2.2±0.6)d], fever [(2.3±0.7)d vs.(3.0±0.9)d]and cough [(5.1±1.2)d vs.(6.7±1.7)d], the hospitalization time [(6.7±1.3)d vs.(8.9±1.9)d]in the observation group were significantly shorter than those in the control group (t=8.778, 3.020, 6.343, 4.008, 5.023, 6.243, all P<0.05). There was no statisticallysignificant difference in the incidence rate of adverse reactions between the two groups(χ2=0.508, P>0.05).@*Conclusion@#The combination of dexamethasone and budesonide in the treatment of acute infectious laryngitis can significantly improve the therapeutic effect, shorten the time of improvement of clinical symptoms, and with high safety, so it is worthy of clinical application.

Effect of continuous venous-venous hemofiltration on patients with severe acute pancreatitis and nursing / 中国实用护理杂志

Objective To observe continuous venous-venous hemofiltration (CVVH) for treatments and cares of severe acute pancreatitis(SAP). Methods From August 2004 to August 2006, 15 cases with SAP were in conventional treatment (the control group), from September 2006 to August 2010, 20 cases with SAP were nursed with CVVH(the observation group). We surveyed patients' vital signs (including body temperature, heart rate, breathing and blood pressure),mental symptoms, abdominal signs and monitored liver and kidney functions. Additionally we executed APACHE Ⅱ scores. We analyzed them retrospectively. Results The afore - mentioned indexes of two groups were significant in statistics, the observation group had lower incidence of MODS、MOF than the control group after 10 days caring. Conclusions The CVVH could correct systemic inflammatory reaction of SAP and prevent complications. Standard technical operation and intensive nursing can ensure smooth process of CVVH and decrease complications caused by CVVH.

Erythrocyte immunity study of intervening 84 cases of ABO maternofetal blood group incompatibility by Yinchenhao Decoction / 中华中医药杂志

Objective: Through treatment based on differentiation of symptoms and signs and classification of defi nited patients of maternofetal blood group incompatibility, detecting anti-A or Anti-B antibody and erythrocyte immune complex chaplet rate(RICR) and erythrocyte receptor chaplet rate(RC3bR) , etc, to observe the therapeutic effect and mechanism of prescriptions mainly with Yinchenhao Decoction. Methods: Patients definited maternofetal blood group incompatibility were divided into control group and observation group according to random principle in 1:3 ratio. Then, observation group was divided into moist heat group(SRG), moist heat and defi ciency of spleen qi group (SR+PQXG) and moist heat and defi ciency of kidney qi group(SR+SQXG) according to syndrome differentiation. Corresponding prescriptions were used, every 30 doses 1 course. Before and after treatment, the anti-A or anti-B antibody and RICR, RC3bR were detected in peripheral blood. Results: In Yinchenhao Decoction group with 21 cases, the anti-A or anti anti-B antibody decreased, including 5 case (1:64) and 4 case (1:32). In group of syndrome differentiation with 63 cases, the anti-A or anti anti-B antibody decreased, including 33 case(1:64) and 20 case (1:32). Before and after treatment, RICR of control group and observation group were(19.43?5.29), (19.57?6.50)and (20.59? 7.96), (23.77?5.12), respectively. RC3bR were(11.62?4.16), (12.42?6.60)and(11.93?4.10), (13.96?6.40)respectively. There was signifi cant difference of before and after treatment in obserbation group(P0.05). Conclusion: In cutting down anti-A and anti-B antibody, and increasing RICR and RC3bR fi eld, the observation groups were better than control group.