BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

The identification of clinical questions for clinical practice guidelines of Chinese patent medicine （CPM） is important for subsequent evidence retrieval， evaluation of evidence quality， formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects， namely， the drug of Chinese patent medicine （D）， the specific disease stage （S）， comparison （C）， and specific outcome （O）， DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research， policy or standard documents， and clinical data are suggested for collecting clinical questions， and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition， the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.

Objective To compare the effect of posterior cruciate ligament retaining(CR)and posterior cruciate substituting(PS)prosthesis in knee arthroplasty.Methods 64 patients with knee osteoarthritis were admitted to our department from June 2021 to June 2022 and whom met the selection criteria were randomly selected and divided into observation group and control group(n = 32).CR prosthesis was used in the observation group,and PS prosthesis was used in the control group.Operation time,postoperative drainage volume,difference of hemoglobin(HGB)before and after operation,postoperative hospital stay,postoperative range of motion at 7 d,14 d,45 d,3 months and 1 year were recorded.ROM,visual analog pain Scale(VAS),Hospital for special surgery(HSS)score,and maximum forward and backward displacement of knee joint and the regular radiographs were also recorded,too.Results The two groups were similar in terms of operation time,postoperative hospital stay,postoperative VAS score and maximum anterior and posterior displacement of knee joint,with P values greater than 0.05,which had no statistical significance.The postoperative drainage volume in the observation group was significantly less than that in the control group,with statistical significance(P＜0.05).The HGB difference of observation group was significantly lower than that of control group,with statistical significance(P＜0.05).There was no statistically significant differ-ence in ROM and HSS scores between the two groups before surgery;the ROM and HSS scores of the control group at 7,14 and 45 days after surgery was better than that of the observation group,with statistical significance(P＜0.05);the ROM and HSS scores of the two groups at 3 months after surgery was not statistically significant.The ROM and HSS scores in the observation group was better than that in the control group at 6 months and 1 year after operation,and the difference was statistically significant(P＜0.05).Conclusions CR prosthesis is superior to PS prosthesis in terms of intraoperative blood loss and post-operative drainage volume,which can reduce surgical risk.Both kinds of prosthesis can achieve good knee stability after surgery,while PS prosthesis has better early clinical effect,while CR prosthesis has better long-term clinical effect.

Objective: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. Methods: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net’s segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. Results: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. Conclusion Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

Objective: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. Methods: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net’s segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. Results: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. Conclusion Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objective To evaluate the risk of bias and reporting quality in randomized controlled trials(RCTs)of the Chinese medicine injection for acute cerebral infarction in the last five years.Methods RCTs literature on Chinese medicine injection in the treatment of acute cerebral infarction was systematically searched in CNKI,Wanfang Data,VIP,China Biology Medicine Database(CBM),PubMed,Embase and Cochrane Library from April 20,2018 to April 20,2023.The risk of bias and reporting quality of included RCTs were evaluated using the Cochrane Risk of Bias Tool(ROB 1.0)and CONSORT-CHM Formulas 2017,respectively.Results A total of 4 301 articles were retrieved,and 408 RCTs were included according to inclusion and exclusion criteria.The ROB evaluation results showed that the the majority of studies were rated as having an unclear risk of bias due to the lack of reporting on allocation concealment,blind method,trial registration information,and funding sources.The evaluation results of CONSORT-CHM Formulas 2017 showed that the number of reported papers of 17 items was greater than or equal to 50%,and the number of reported papers of 25 items was less than 10%,and most of the RCTs did not show the characteristics of TCM syndrome differentiation and treatment.Conclusion The quality of Chinese medicine injection in the treatment of acute cerebral infarction RCTs is generally low.It is recommended that researchers refer to the methodology design of RCTs and international reporting standards,improve the trial design,standardize the trial report,and highlight the characteristics of TCM syndrome differentiation and treatment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective We investigated the effects of ICAM5 in the hippocampus on the alcohol drinking preference of mice,and the potential mechanisms.Methods An alcohol two-bottle choice model was developed in 8-week-old male C57BL/6J mice,which were randomly divided to two groups:water group and alcohol group.The protein expression of ICAM5 in the hippocampus,amygdala,and medial prefrontal cortex was detected.An ICAM5-overexpressing adeno-associated virus was constructed and injected into the hippocampus by stereotaxic method.The expression level of ICAM5 protein in the hippocampus was detected by immunofluorescence and Western blot.We then detected the alcohol preference and locomotor activity of mice with a conditioned place preference(CPP)experiment,open field test,and loss-of-righting reflex test.Western blot analysis was used to identify the neuron F-actin/G-actin ratio.Using Golgi staining,the morphology of dendritic spines was identified.Results The expression of ICAM5 in the hippocampus of alcohol two-bottle choice model mice in the alcohol group was considerably lower than that of the water group(P＜0.001).The specific expression of ICAM5 in the hippocampus of mice was observed by fluorescence microscopy.In the open field experiment,the staying time and moving distance of the AAV-ICAM5 group were significantly increased compared with those of the control group(P＜0.01).In the CPP experiment,the residence time of AAV-ICAM5 mice in the alcohol-paired compartment was significantly lower than that of control mice(P＜0.001).In the loss-of-righting reflex experiment,overexpression of ICAM5 significantly reduced sedation latency(P＜0.01),but significantly shortened the duration of sedation(P＜0.001).Compared with AAV-mCherry+Water group,the ratio of F-actin/G-actin in the hippocampus was significantly increased after drinking(P＜0.01),but after ICAM5 overexpression,their F-actin/G-actin ratio was significantly decreased(P＜0.001).Compared with AAV-mCherry+Water group,the density of dendritic spines in the hippocampal CAI region was increased(P＜0.001),but the density of dendritic spines in the AAV-ICAM5+Alcohol group was significantly decreased(P＜0.01).Conclusions ICAM5 modulated the expression of cytoskeleton proteins to change the structural plasticity of dendritic spines,which contributed to alcohol-drinking and locomotor behavioral changes in mice.

AIM:To investigate the impact of hippocampal protein phosphatase 1 regulator subunit 17(Ppp1r17)down-regulation on drinking-related behavior in mice,and to explore the protein kinase B(PKB/AKT)/glyco-gen synthase kinase-3β(GSK-3β)/cAMP response element binding protein(CREB)signaling pathway of Ppp1r17 in the development of alcohol dependence.METHODS:Forty male C57BL/6J mice were randomly divided into four groups(n=10):control group,shPpp1r17① group,shPpp1r17② group and shPpp1r17③ group.The mRNA and protein expression levels in the hippocampal tissues were evaluated after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into a control group and a shPpp1r17 group(n=10).An open-field test,conditioned place prefer-ence(CPP)test and righting reflex test were performed.Furthermore,the localization and expression of AAV-shPpp1r17 were detected after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into four groups(n=5):the empty virus+water group,the empty virus+EtOH group,the shPpp1r17+water group and the shPpp1r17+EtOH group.The EtOH group mice drank 9%alcohol continuously for 30 d.The protein expression levels of Ppp1r17,p-AKT,AKT,p-GSK-3β,GSK-3β,p-CREB and CREB were detected by Western blot.RESULTS:(1)The results of qPCR showed that Ppp1r17 was successfully suppressed by shPpp1r17.(2)The behavioral results showed that the shPpp1r17 group mice exhibited enhanced exercise ability and reduced anxiety-like emotions,and the downregulation of Ppp1r17 increased CPP scores and reduced the sensitivity of the mice to alcohol.(3)Immunofluorescence showed that AAV-shPpp1r17 was specifically expressed in the hippocampus.(4)Western blot analysis revealed that Ppp1r17 and the p-AKT/AKT,p-GSK-3β/GSK-3β and p-CREB/CREB ratios were significantly increased after treatment of EtOH.Howev-er,the protein expression of Ppp1r17 was significantly reduced,and the AKT/GSK-3β/CREB pathway was activated after knockdown of Ppp1r17 in the hippocampus.CONCLUSION:Ppp1r17 may suppress CREB phosphorylation through the AKT/GSK-3β/CREB pathway,thereby influencing alcohol drinking preference and locomotor behavior in mice.