Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification.

BACKGROUND: Disorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells. METHODS: The HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests. RESULTS: We have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca2+ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage. CONCLUSION: Gastrodin has neuroprotective effects against glutamate-induced neurotoxicity.

Configurational Paths of Preconditions to Transformational Leadership Among Core Hospital Leaders: A Fuzzy-Set Qualitative Comparative Analysis.

Purpose: Transformational leadership among core hospital leaders boosts medical organizations' competitiveness, adaptability, and sustainability, which is jointly affected by individual, organizational and environmental factors. This study aims to unpack its configurational framework and propose strategies to strengthen core hospital leaders' transformational leadership. Patients and Methods: Data were collected from an online questionnaire among 31 core hospital leaders. The fuzzy-set qualitative comparative analysis (fsQCA) was used to explore the causal mechanism of high-level transformational leadership. We enrich this mechanism by professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure. Results: Result shows initiative spirit is the only necessary condition (consistency=0.911) for the formation of high-level transformational leadership among core hospital leaders. Three configurations are the sufficient conditions that lead to high-level transformational leadership among core hospital leaders with two different professional backgrounds (overall solution consistency= 0.952). Conclusion: Core hospital leaders' initiative spirit is an indispensable condition for improving high-level transformational leadership, emphasizing the necessity for core leaders to be proactive in order to develop such leadership. Besides, the study also uncovered three configurations are the sufficient conditions for core hospital leaders with diverse professional backgrounds to achieve high-level transformational leadership. This finding offers significant insights into hospital management practices, suggesting that core hospital leaders' work should be managed in a personalized manner based on their professional backgrounds, thereby fostering favorable conditions conducive to the development of their high-level transformational leadership capabilities. Furthermore, the central insight of this study is that the formation of high-level transformational leadership contingent upon the collaboration of professional background, critical thinking, initiative spirit, family-work conflict, job satisfaction, subordinates' followership, and work pressure, contributing to a holistic and more rigorous view for the development of transformational leadership.

Effectiveness of specialist nurse-led WeChat mini program management for disease control in asthma: A randomized controlled study.

BACKGROUND: Asthma is a common chronic respiratory disease in childhood, requiring effective management strategies. PURPOSE: This study aims to evaluate the effectiveness of a nurse-led WeChat Mini Program in managing asthma among children aged 6 to 11 years. METHODS: This randomized controlled trial adhered to the CONSORT checklist and was conducted at a tertiary hospital in China from January 2023 to August 2023. One hundred and eight children with asthma were randomly assigned to two groups, and 81 children completed the 6-month follow-up. All participants received asthma management from specialist nurses, including routine treatments such as inhaled corticosteroids. The experimental group also utilized the WeChat Mini Program for asthma management. Both groups underwent follow-up assessments at 3 and 6 months post-enrollment, which included the Childhood Asthma Control Test (C-ACT), asthma control levels, frequency of exacerbations, and lung function. RESULTS: At 3 and 6 months, the experimental group showed significantly higher C-ACT scores and a lower exacerbation frequency compared to the control group (p < 0.05). While Peak Expiratory Flow improved, Forced Expiratory Volume in 1 Second Percentage Predicted (FEV1%) and FEV1/FVC did not change significantly. CONCLUSIONS: The WeChat Mini Program significantly improved asthma control and reduced exacerbations but did not substantially enhance all lung function parameters. Further research is required to confirm its long-term effects. APPLICATION TO PRACTICE: Incorporating a specialist nurse-led digital management tool, such as the WeChat Mini Program, into standard pediatric asthma care may offer an effective management strategy.

Effectiveness of Paxlovid in the treatment of the SARS-CoV-2 Omicron variant infection in children with hematologic malignancies: a retrospective cohort study.

Background: Patients with hematologic malignancies (HMs) may be immunocompromised after receiving anti-tumor therapy. Those who also have the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection face many challenges, including a lack of effective antiviral drugs. This study aimed to investigate the clinical features of the SARS-CoV-2 Omicron variant infection in children with HMs, and the effectiveness of Paxlovid. Methods: A retrospective, non-randomized study was conducted on pediatric patients with HMs infected with the SARS-CoV-2 Omicron variant who had been admitted to the Shanghai Children's Medical Center, Shanghai, China from December 1, 2022 to March 1, 2023. The Paxlovid-treated group (Group P) comprised 21 patients, and the non-Paxlovid-treated group (Group N) comprised 21 patients. The patients' demographic data, clinical features, and therapeutic outcomes were collected. Statistical tests were used to evaluate the effectiveness of the treatment and related factors. Results: The clinical course of the SARS-CoV-2 Omicron variant infection for most of the children with HMs was non-severe (97.6%), and only one child progressed to severe disease (2.4%). The most common symptoms were fever (66.7%) and cough (52.4%). Compared with the children in Group N, those in Group P had worse clinical characteristics, including those who previously underwent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T (CAR-T) cell treatment (71.4% vs. 28.6%, P=0.005), and those in the myelosuppressive phase (57.1% vs. 4.8%, P<0.001). Most of the children in Group P were treated with more than two types of antibiotics (76.2% vs. 42.9%, P=0.02). The patients treated with Paxlovid within 5 days of diagnosis had a median viral clearance time of 5 days [interquartile range (IQR), 4-8 days], which was significantly shorter than that of the patients who were not treated with Paxlovid (P=0.03). There were no significant differences in the clinical outcomes between the two groups after the propensity score matching (PSM) analyses. Eight patients (19%) had repeat-positive (re-positive) test results. No factor was found to be statistically significant in predicting re-positive test results based on the binary logistic regression analysis. Conclusions: Administering Paxlovid within 5 days of the diagnosis of the SARS-CoV-2 Omicron variant infection in children may effectively shorten the clearance time of the virus, but there is still the possibility the patients may have re-positive test results.

Impact of PM2.5 exposure in old age and its interactive effect with smoking on incidence of diabetes.

PURPOSE: To determine the impact of PM2.5 exposure in old age and its interactive effect with smoking on incident diabetes. METHODS: A total of 2766 participants aged ≥60 years in China were interviewed at baseline for disease risk factors in 2001-03 and were then followed up for 10 years to document incident diabetes. They were assessed for daily PM2.5 exposure in 2005. Multivariate Cox regression models were used to examine the association of PM2.5 exposure with incident diabetes and interactive effect between PM2.5 and smoking on incident diabetes. RESULTS: During the cohort follow-up, 176 participants developed diabetes. The incidence of diabetes increased with PM2.5 exposure; the multiple-adjusted hazard ratio (HR) of diabetes was 2.27 (95 % CI 1.36-3.77) in participants with PM2.5 at ≥62.0 µg/m3 compared to those at <62.0 µg/m3. There was a significant interaction effect of PM2.5 with smoking on increased risk of diabetes. The adjusted HR for participants exposed to PM2.5 levels ≥62.0 µg/m3 who smoked was 4.39 (95 % CI 1.72-11.21), while for non-smokers it was 1.65 (95 % CI 0.88-3.09), compared to those at <62.0 µg/m3. CONCLUSIONS: Exposure to PM2.5 in old age was associated with an increased incidence of diabetes and smoking enhanced the impact of PM2.5 on diabetic risk. These findings underscore the urgent need for air quality improvement measures and smoking cessation programs to mitigate the risk of diabetes in aging populations.

Effect of pectineus muscle plane block versus femoral nerve block for postoperative analgesia and early recovery after knee surgery: a randomised controlled trial study protocol.

BACKGROUND: Femoral nerve block (FNB) is a prevalent method used for postoperative pain management after knee surgery; however, it decreases the strength of the quadriceps muscle and is not conducive to early recovery after surgery. Pectineus muscle plane (PMP) block involves the injection of a local anaesthetic into the fascial plane below the pectineus muscle, where it blocks the obturator and saphenous nerves. However, there is little evidence on the effectiveness of PMP block for analgesia after knee surgery. The aim of this trial is to assess whether PMP block can improve postoperative analgesia, promote early recovery and reduce the length of hospital stay. METHODS AND ANALYSIS: In this randomised controlled study, 46 patients will be randomly allocated into two groups: the PMP block group (n=23) and the FNB group (n=23). The primary outcome measures will include Visual Analog Scale scores for pain at rest and during movement at various time points following knee surgery. Secondary outcomes will include the degree of active flexion, straight leg raise test performance, get-out-of-bed test result, 20 m walk test result, total dose administered via patient-controlled analgesia infusion pumps, hospital stay duration, patient satisfaction and postoperative complications, such as pulmonary embolism and deep vein thrombosis.This study protocol adheres to rigorous standards for ethical conduct and patient safety. The findings from this trial are expected to contribute valuable insights to the optimisation of postoperative pain management strategies and the improvement of early recovery outcomes for patients who undergo knee surgery. ETHICS AND DISSEMINATION: This trial has been approved by the ethics committee of Zhejiang Hospital (2022(128K)) on 17 November 2022, and inpatients who meet the inclusion criteria and diagnostic requirements are eligible for this study. Any subsequent protocol and informed consent document amendments must be approved by the responsible ethics committee. All communications with the regulatory authorities and the ethics committee must be recorded. All recruited patients will be informed of the trial purposes and their duties within the trial before randomisation. Recruited patients can withdraw from the study at any time without providing any specific reason. The patient data will be stored in a separate, safe place, but that it may be reviewed by the relevant investigator. The results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR2300076018. Registered on 21 September 2023.

Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms.

Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.

Enhanced in situ H2O2 electrosynthesis and leachate concentrate degradation through side-aeration and modified cathode in an electro-Fenton system.

The active graphite felt (GF) catalytic layer was effectively synthesized through a wet ultrasonic impregnation-calcination method, modified with CB and PTFE, and implemented in a pioneering side-aeration electrochemical in-situ H2O2 reactor. The optimal mass ratio (CB: PTFE 1:4) for the modified cathode catalytic layer was determined using a single-factor method. Operating under optimum conditions of initial pH 5, 0.5 L/min air flow, and a current density of 9 mA/cm2, the system achieved a remarkable maximum H2O2 accumulation of 560 mg/L, with the H2O2 production capacity consistently exceeding 95 % over 6 usage cycles. The refined mesoporous structure and improved three-phase interface notably amplified oxygen transfer, utilization, and H2O2 yield. Side aeration led to an oxygen concentration near the cathode reaching 20 mg/L, representing a five-fold increase compared to the 3.95 mg/L achieved with conventional bottom aeration. In the final application, the reaction system exhibited efficacy in the degradation of landfill leachate concentrate. After a 60-minute reaction, complete removal of chroma was attained, and the TOC degradation rate surpassed 60 %, marking a sixfold improvement over the conventional system. These results underscore the substantial potential of the system in H2O2 synthesis and environmental remediation.

Recommendations for the selection of nucleoside analogues as antihuman herpesvirus drugs: a real-world analysis of reported cases from the FDA adverse event reporting system.

OBJECTIVE: The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings. METHODS: Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining. RESULTS: A total of 18,591, 24,206, 6,150, and 419 reports of ADEs associated with acyclovir (ACV), valacyclovir (VACV), ganciclovir (GCV), and famciclovir (FCV) were screened and extracted from the FAERS. In this study, the report summarized the high frequency and strong correlation of ADEs for the four drugs at the Preferred Term (PT) level. Additionally, the analysis also identified the relationship between ADEs and factors such as age, gender, and severity of outcome at the System Organ Class (SOC) level. CONCLUSION: The safety reports for the four-nucleoside analogue anti-herpesvirus drugs are diverse and interconnected. Dosing for patients with herpesvirus infections should be tailored to their specific conditions and the potential risk of disease.

TCRαß-depleted hematopoietic stem cell transplant and third-party CD45RA+ depleted adoptive cell therapy for treatment of post-transplant parvovirus B19 aplastic crisis.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαß+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαß+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death.

Vascular endothelial cells play a critical role in maintaining the health of blood vessels, but dysfunction can lead to cardiovascular diseases. The impact of arsenite exposure on cardiovascular health is a significant concern due to its potential adverse effects. This study aims to explore how NBR1-mediated autophagy in vascular endothelial cells can protect against oxidative stress and apoptosis induced by arsenite. Initially, our observations revealed that arsenite exposure increased oxidative stress and triggered apoptotic cell death in human umbilical vein endothelial cells (HUVECs). However, treatment with the apoptosis inhibitor Z-VAD-FMK notably reduced arsenite-induced apoptosis. Additionally, arsenite activated the autophagy pathway and enhanced autophagic flux in HUVECs. Interestingly, inhibition of autophagy exacerbated arsenite-induced apoptotic cell death. Our findings also demonstrated the importance of autophagy receptor NBR1 in arsenite-induced cytotoxicity, as it facilitated the recruitment of caspase 8 to autophagosomes for degradation. The protective effect of NBR1 against arsenite-induced apoptosis was compromised when autophagy was inhibited using pharmacological inhibitors or through genetic knockdown of essential autophagy genes. Conversely, overexpression of NBR1 facilitated caspase 8 degradation and reduced apoptotic cell death in arsenite-treated HUVECs. In conclusion, our study highlights the vital role of NBR1-mediated autophagic degradation of caspase 8 in safeguarding vascular endothelial cells from arsenite-induced oxidative stress and apoptotic cell death. Targeting this pathway could offer a promising therapeutic approach to mitigate cardiovascular diseases associated with arsenite exposure.

Droplet digital PCR: An effective method for monitoring and prognostic evaluation of minimal residual disease in JMML.

Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)-monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1- to 3-month window post-HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post-HSCT was observed, as 65% (13/20) of non-relapse patients took over 6 months to achieve ddPCR-MRD negativity. Furthermore, bone marrow ddPCR-MRD levels at 1-month post-HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR-MRD levels at this time point (p = 0.026), with a cut-off of 0.465% effectively stratifying overall survival (p = 0.007), event-free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR's superiority in JMML MRD monitoring post-HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML.

Ultrasound-Based Deep Learning Radiomics Nomogram for the Assessment of Lymphovascular Invasion in Invasive Breast Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. RESULTS: The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90-0.95), 0.91 (95% CI 0.87-0.95), and 0.91 (95% CI 0.86-0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. CONCLUSION: The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions.

Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism.

The taste and tenderness of meat are the main determinants of carcass quality in many countries. This study aimed to discuss the mechanisms of intramuscular fat deposition in grazing and house-breeding cattle. We performed transcriptome analysis to characterize messenger RNA and microRNA (miRNA) expression profiles. A total of 456 and 66 differentially expressed genes (DEGs) and differentially expressed (DE) miRNAs were identified in the adipose tissue of grazing and house-breeding cattle. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the association of DEGs with fatty acid metabolism, fatty acid degradation, peroxisome proliferator-activated receptors signaling pathway, adenosine monophosphate-activated protein kinase signaling pathway, adipocytokine signaling pathway, and the association of DE miRNAs with mitogen-activated protein kinase signaling pathway. Apolipoprotein L domain containing 1, pyruvate dehydrogenase kinase 4, and sphingosine-1-phosphate lyase 1 genes may be the key regulators of fat metabolism in grazing cattle. Finally, we found that miR-211 and miR-331-5p were negatively correlated with the elongation of very long-chain fatty acids protein 6 (ELOVL6), and miR-331-5p might be the new regulator involved in fat metabolism. The results indicated that ELOVL6 participated in various functions and pathways related to fat metabolism. Meanwhile, miR-331-5p, as a new regulator, might play an essential role in this process. Our findings laid a more in-depth and systematic research foundation for the formation mechanism and characteristics of adipose tissue in grazing cattle.

Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia.

Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potency in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.

Evaluation of innovation primacy in cross-regional central cities: Evidence from the Huaihai Economic Zone in China (2010-2020).

With the intensification of global economic competition, innovation has become one of the core elements of vigorous development in various regions. Improving the innovation ability of cross-regional central cities is the main factor influencing whether a region can achieve economic and social development. In this paper, an innovation primacy index system is designed according to the links of the innovation value chain, and the innovation advantages and empirical effects are comprehensively analyzed by using the point-to-point method, entropy weight method, gravity model and two-way fixed effect model. Based on the data of 8 cities in the core area of the Huaihai Economic Zone from 2010 to 2020 in China, Xuzhou's innovation primacy ranks first in the core area of the Huaihai Economic Zone, which accords with its status as the central city of the region. Its index has been rising, and its development trend is also good. However, the overall innovation ability of the core area of the Huaihai Economic Zone is unbalanced; the overall economic foundation is not solid enough. In terms of knowledge innovation, R&D innovation and industrial innovation, the industrialization level, around the activation of Xuzhou city vitality, enhances the Xuzhou innovation radiation drive, leading to a decrease in the Huaihai Economic Zone. Finally, some corresponding suggestions on innovation primacy have been proposed for the city of the Huaihai Economic Zone.

The Characterization of Subcutaneous Adipose Tissue in Sunit Sheep at Different Growth Stages: A Comprehensive Analysis of the Morphology, Fatty Acid Profile, and Metabolite Profile.

Adipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.

A meta-analysis of the implementation of enhanced recovery after surgery pathways in anterior cervical spine surgery for degenerative cervical spine diseases.

OBJECTIVE: To systematically evaluate the perioperative effects of enhanced recovery after surgery (ERAS) protocol on anterior cervical spine surgery by means of meta-analysis. METHODS: According to the PRISMA guidelines, the article's search on the China National Knowledge Infrastructure (CNKI), Wanfang data resource system, VIP, PubMed database and Cochrane library was conducted to identify clinical studies investigating the effects of ERAS protocols on anterior cervical spine surgery. A quantitative meta-analysis was performed for the clinical outcomes extracted from the studies that met inclusion criteria. RESULTS: Of the 21 studies identified from the article search, 10 studies met inclusion criteria. The meta-analysis showed shorter length of stay (LOS) (MD = -2.16, 95% CI (-2.57, -1.75), P < 0.00001) and higher patient satisfaction for the ERAS protocols (OR = 3.13, 95% CI (1.97, 4.98), P < 0.00001). Furthermore, ERAS programs led to significant decreases in cost (MD = -0.81, 95% CI (-1.08, -0.53), P < 0.00001) and complication rates (OR = 0.15, 95% CI (0.08, 0.27), P < 0.00001), but no difference in 90-day readmission (OR = 0.63, 95% CI (0.30, 1.35), P = 0.24). CONCLUSIONS: The data of this study suggest that the implementation of ERAS protocol decreases LOS, cost and complications rates and improve satisfaction for the patients undergoing anterior cervical spine surgery. To support the practice use of ERAS in anterior cervical spine surgery further, controlled trials will be indispensable.

Integrated Transcriptome Analysis of miRNAs and mRNAs in the Skeletal Muscle of Wuranke Sheep.

MicroRNAs (miRNAs) are regarded as important regulators in skeletal muscle development. To reveal the regulatory roles of miRNAs and their target mRNAs underlying the skeletal muscle development of Wuranke sheep, we investigated the miRNA and mRNA expression profiles in the biceps femoris of these sheep at the fetal (3 months of gestation) and 3- and 15-month-old postnatal stages. Consequently, a total of 1195 miRNAs and 24,959 genes were identified. Furthermore, 474, 461, and 54 differentially expressed miRNAs (DEMs) and 6783, 7407, and 78 differentially expressed genes (DEGs) were detected among three comparative groups. Functional analysis demonstrated that the target mRNAs of the DEMs were enriched in multiple pathways related to muscle development. Moreover, the interactions among several predicted miRNA-mRNA pairs (oar-miR-133-HDAC1, oar-miR-1185-5p-MYH1/HADHA/OXCT1, and PC-5p-3703_578-INSR/ACTG1) that potentially affect skeletal muscle development were verified using dual-luciferase reporter assays. In this study, we identified the miRNA and mRNA differences in the skeletal muscle of Wuranke sheep at different developmental stages and revealed that a series of candidate miRNA-mRNA pairs may act as modulators of muscle development. These results will contribute to future studies on the function of miRNAs and their target mRNAs during skeletal muscle development in Wuranke sheep.

Case Report: Unedited allogeneic chimeric antigen receptor T cell bridging to conditioning-free hematopoietic stem cell transplantation for a child with refractory Burkitt lymphoma.

Purpose: Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin's lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course chemotherapies have achieved a good effect, refractory/relapsed BL has a poor prognosis with cure rates less than 30%. Chimeric antigen receptor T cell (CAR-T) therapy has developed rapidly in recent years and achieved excellent results in acute lymphoblastic leukemia (ALL). However, in some cases, there is a failure to produce autologous CAR-T cells because of T-cell dysfunction. In such cases, allogeneic CAR-T therapy has to be considered. Methods: A 17-year-old boy with stage II BL did not respond to extensive chemotherapy and sequential autologous CAR-T therapy. Lentiviral vectors containing anti-CD20-BB-ζ (20CAR) and anti-CD22-BB-ζ (22CAR) transgenes were used to modify the T cells from an HLA-identical matched unrelated donor. Flow cytometry was used to assess the cytokine analyses and CAR-T cell persistence in peripheral blood, enumerated by qPCR as copies per ug DNA. Informed consent for autologous/allogeneic CAR-T therapy was obtained from the patient and his legal guardian. Results: Unedited HLA-matched allogeneic CD20 and CD22 CAR-T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. Because of persistent pancytopenia and full donor chimerism, the same donor's conditioning-free peripheral blood stem cells were successfully transplanted 55 days post CAR-T. Neutrophils were engrafted at day +11 and platelets were rebuilt at day +47 without obvious acute graft-versus-host disease (GVHD), but there was mild chronic GVHD in the skin and eyes. Currently, active anti-rejection therapy is still underway. Conclusion: Unedited HLA-matched allogeneic CAR-T cell therapy could be an innovative, effective, and safe treatment for children with refractory/relapse BL without obvious acute GVHD. Conditioning-free allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor is feasible for a patient with full donor T-cell chimerism after allogeneic CAR-T. It cannot be ignored that close GVHD monitoring is needed post HSCT.