BACKGROUND:Stroboscopic visual training can force sensory reweighting to restore the original weights by increasing sensitivity to proprioceptive information,which may be an effective method to improve proprioception. OBJECTIVE:To determine the effects of balance training in three conditions,low frequency,high frequency and normal vision,on ankle proprioception in patients with chronic ankle instability. METHODS:Thirty-six patients with chronic ankle instability recruited from the students of Southwest Medical University were randomly assigned to a low-frequency vision training group,a high-frequency vision training group,and a normal vision training group,with 12 subjects in each group.Subjects in the three groups underwent progressive hop stabilization and balance training,in which the low-frequency vision training group and the high-frequency vision training group wore stroboscopic spectacles during the training,with a stroboscopic frequency of 1.75 and 5 Hz,respectively.The training in each group was performed three times a week for 4 consecutive weeks.Assessments,including ankle proprioception,ankle stability self-assessment and dynamic postural stability,were performed before training and within 1 week after the completion of training. RESULTS AND CONCLUSION:There was a significant main effect of time factor in ankle proprioception(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvement in ankle proprioception after 4 weeks of training(P<0.05);and subjects in the low-frequency vision training group showed a significant improvement in ankle proprioception compared with that of the normal vision training group after 4 weeks of training(P<0.05).There were significant main effects of time factor and group×time interaction in ankle proprioception(P<0.05).Compared with the pre-training period,the ankle stability self-assessment in all three groups was improved after 4 weeks of training(P<0.05).And the ankle stability self-assessment in high-frequency visual training group was higher than that in normal vision training group after 4 weeks of training(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvements in forward dynamic postural stability,posteromedial dynamic postural stability,and posterolateral dynamic postural stability after 4 weeks of training(P<0.05),while in the normal vision training group,forward dynamic postural stability and posterolateral dynamic postural stability were significantly improved after 4 weeks of training(P≤0.05).To conclude,balance training under stroboscopic visual conditioning improves proprioception,ankle stability self-assessment,and dynamic postural stability in patients with chronic ankle instability regardless of frequency.

Objective To observe and compare in-hospital and 1-year survival and prognosis of patients with 4b acute myocardial infarction(AMI)caused by early and late stent thrombosis(ST).Methods A total of 302 patients with 4b acute myocardial infarction caused by ST were enrolled in this study from January 2015 to February 2018.ST patients were confirmed by coronary angiography.These patients were divided into two groups:the early ST group(n=26)and the late ST group(n=276)according to the time of ST occurrence.Endpoint events during hospitalization and one year of follow up were compared between the two groups of patients.The primary endpoint events included cardiac death and recurrent AMI.The secondary endpoint events included target lesion revascularization(TLR),re-stent thrombosis,heart failure and stroke.The incidence of no endpoint events was compared between two groups of patients by Kaplan and Meier survival analysis.Cox regression analysis was used to analyze risk factors for endpoint events in patients with type 4b AMI.Results There was no significant difference in the incidence of the primary endpoint events during hospitalization between the two groups(7.7%vs.3.3%,P=0.243).The incidence of heart failure was higher in the early ST group than that of the late ST group(11.5%vs.1.4%,P=0.016).There was no significant difference in the incidence rates of other secondary endpoint events between the two groups(P＞0.05).After a mean follow-up of 1 year,the incidence rates of primary endpoint events and the secondary eendpoint events were higher in the early ST group(20.0%vs.5.9%,P＜0.05 and 36.0%vs.11.5%,P＜0.01)than that of the late ST group.Kaplan and Meier survival analysis showed that the 1-year cumulative incidences of non-primary(P= 0.022)and non-secondary events(P＜0.001)were lower in the early ST group than those of the late ST group.Cox regression analysis showed that hypertension and history of coronary artery bypass grafting were independent risk factors for primary endpoint events in patients with 4b AMI,and intraoperative implantation of intraaortic balloon pump(IABP)and shortening the time from stent thrombosis to balloon dilation(ST to B)were independent protective factor.Conclusion Early ST patients have similar in-hospital outcomes and poor long-term prognosis compared with late ST induced 4b type AMI patients.Intraoperative implantation of IABP and shortening of ST to B time may improve the prognosis of 4b type AMI patients.

Objective:To evaluate the efficacy and outcomes of early removal of lumen-apposing metal stent (LAMS) in the treatment of pancreatic wall-off necrosis (WON).Methods:A retrospective analysis was performed on 51 patients with WON who underwent endoscopic ultrasound (EUS)-guided transluminal drainage (ETD) and direct endoscopic necrosectomy (DEN) using LAMS at Nanjing Drum Tower Hospital from January 2018 to December 2022. Patients were divided into the early removal group (within two weeks, n=24) and the traditional removal group (after two weeks, n=27) based on the timing of LAMS removal. The short-term effects, safety and long-term outcomes of WON were compared between the two groups. Results:The technical success rate of LAMS placement in 51 patients reached 100%, and all patients underwent ETD and DEN. The median number of necrosectomy sessions in the early removal group was significantly lower than in the traditional removal group, 2.0 sessions vs 3.0 sessions and the difference was statistically significant ( P<0.05). Postoperatively, 15.7% of patients required percutaneous catheter drainage (PCD) and 5.9% required surgery, with no significant difference between the two groups. The clinical success rate and mortality rate in the early removal group were 79.2% and 8.3%, respectively, compared to 81.5% and 3.7% in the traditional removal group, with no statistically significant difference. In terms of safety, the early removal group exhibited a significantly lower rate of adverse events during stent retention with statistically significant difference (12.5% vs 37.0%, P<0.05) compared to the traditional removal group. A total of 46 patients were followed up for six months. In the early removal group, the rates of disease recurrence, need for endoscopic reintervention and occurrence of long-term complications were 20.0%, 10.0% and 20.0%, respectively. These rates did not show a significant increase compared to the traditional removal group, which were 7.7%, 3.8% and 38.5%, respectively, without significant differences between the groups. Conclusions:In the treatment of WON, early removal of LAMS is safe and effective to a certain extent. In comparison to the traditional practice of removing LAMS after two weeks, early removal does not reduce clinical success rates, nor does it increase the rates of disease-related mortality, recurrence, or long-term complications. On the contrary, it may reduce the occurrence of adverse events during stent retention and decrease the number of necrosectomy procedures subsequently.

Objective:To establish the best evidence-based approach for early fluid resuscitation management in patients with severe acute pancreatitis (SAP).Methods:A literature search was conducted utilizing evidence-based nursing methods to identify relevant evidence on the management of early fluid resuscitation in patients with SAP. The search followed the hierarchical order of the " 6S" evidence pyramid, including databases such as China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (SinoMed), Wanfang Database, UpToDate, NICE, RNAO Guidelines Network, Pancreatology International, WHO Association Website, JBI, Cochrane, PubMed, EMBASE, and CINAHL. The search was limited to articles published from the establishment of each database to March 2022. The literature quality evaluation tools and an evidence pre-grading system from the JBI Evidence-Based Health Care Center were employed to assess the quality of the literature included in the study. Additionally, the FAME structure was utilized to evaluate the feasibility, appropriateness, clinical significance, and validity of the evidence.Results:Nine articles were finally incorporated into the analysis, including four guidelines, one evidence summary, two systematic reviews, and two expert consensus articles. 21 pieces of evidence pertaining to early fluid resuscitation management in patients with SAP was summarized, encompassing five key aspects: resuscitation timing, type of fluid infusion, total volume and speed of fluid infusion, dynamic monitoring, and fluid resuscitation goals. It was advisable for patients diagnosed with SAP to promptly receive fluid resuscitation, ideally within 72 hours of diagnosis. The initial choice for fluid resuscitation was lactated Ringer′s solution, with the addition of human albumin as a supplementary colloid solution. The quantity of fluid administered within the first 24 hours of rehydration should constitute approximately 33.3% of the total rehydration volume within the 72 hours time-frame. In the case of patients experiencing early shock or dehydration, it was advised that the fluid rate administered should be 5-10 ml·kg -1·h -1 within the first 24 hours of admission. Additionally, an infusion of 20 ml/kg of fluid can be administered within the initial 30-45 minutes. It was recommended to assess the adequacy of early fluid resuscitation every 4-6 hours, ensuring that the resuscitation objective could meet at least two of the following criteria: urine output of 0.5-1 ml·kg -1·h -1, mean arterial pressure of 65-85 mmHg, central venous pressure of 8-12 mmHg, heart rate below 120 beats/min, central venous oxygen saturation of at least 70%, and a decrease in hematocrit levels to 30%-35%. Conclusions:The most compelling evidence supporting the implementation of early fluid resuscitation management in patients with SAP is derived from an evidence-based nursing approach, which could effectively improve patient care outcomes.

Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.

Objective:To evaluate the effect of dexmedetomidine on the expression of DNA methyltransferases in septic mice with acute lung injury.Methods:Forty-eight clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation + dexmedetomidine group(group Sham+ DEX), sepsis group (group Sepsis) and sepsis + dexmedetomidine group(group Sepsis+ DEX). Sepsis model was established by cecal ligation and puncture(CLP)in anesthetized mice. At 30 min before model preparation, dexmedetomidine 0.05 μg/g (in 0.5 ml of normal saline) was administered in Sham + DEX and Sepsis + DEX groups, and normal saline 0.5 ml was given instead in Sham and Sepsis groups. The mice were sacrificed at 24 h after CLP, and the lung tissue was taken to determine the wet to dry lung weight ratio, contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and high mobility group box-1 (HMGB-1), activities of superoxide dismutase (SOD) and myeloperoxidase (MPO), and content of malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), global DNA methylation (by colorimetric assay), and expression of DNA methyltransferases (DNMTl, DNMT3a, DNMT3b) (by Western blot) and to examine the histopathological changes of lung tissues (by HE staining) which were scored. Results:Compared with group Sham, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly increased, SOD activity was decreased, and the expression of DNMT1 and DNMT3a was up-regulated in group Sepsis and group Sepsis+ DEX ( P<0.05), and no significant change was found in the aforementioned indexes in group Sham+ DEX ( P>0.05). Compared with group Sepsis, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly decreased, SOD activity was increased, and the expression of DNMT1 and DNMT3a was down-regulated in group Sepsis+ DEX ( P<0.05). Conclusions:The mechanism by which dexmedetomidine reduces acute lung injury is related to inhibition of up-regulation of DNMT1 and DNMT3a expression in septic mice.

Objective: Network pharmacology combines drug and disease targets with biological information networks based on the integrity and systematicness of the interactions between drugs and disease targets. This study aims to explore the molecular basis of Hanshi Zufei formula for treatment of COVID-19 based on network pharmacology and molecular docking techniques. Methods: Using TCMSP, the chemical constituents and molecular targets of Atractylodis Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Pogostemonis Herba, Tsaoko Fructus, Ephedrae Herba, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, and Arecae Semen were investigated. The predicted targets of novel coronavirus were screened using the NCBI and GeneCards databases. To further screen the drug-disease core targets network, the corresponding target proteins were queried using multiple databases (Biogrid, DIP, and HPRD), a protein interaction network graph was constructed, and the network topology was analyzed. The molecular docking studies were also performed between the network's top 15 compounds and the coronavirus (SARS-CoV-2) 3CL hydrolytic enzyme and angiotensin conversion enzyme II (ACE2). Results: The herb-active ingredient-target network contained nine drugs, 86 compounds, and 49 drug-disease targets. Gene ontology (GO) enrichment analysis resulted in 1566 GO items (P < 0.05), among which 1438 were biological process items, 35 were cell composition items, and 93 were molecular function items. Fourteen signal pathways were obtained by enrichment screening of the KEGG pathway database (P < 0.05). The molecular docking results showed that the affinity of the core active compounds with the SARS-CoV-2 3CL hydrolase was better than for the other compounds. Conclusion: Several core compounds can regulate multiple signaling pathways by binding with 3CL hydrolase and ACE2, which might contribute to the treatment of COVID-19.

Objective:To evaluate the efficacy of transgastric combined with percutaneous endoscopic treatment for infected pancreatic necrosis (IPN).Methods:Clinical data of 19 IPN patients who received transgastric combined with percutaneous endoscopy at the Gastroenterology Intensive Care Unit of Nanjing Drum Tower Hospital from August 2015 to August 2020 were retrospectively studied. The clinical efficacy and the procedure-related complications were analyzed.Results:The mean procedure of endoscopic transmural drainage (ETD) was 1.1±0.3 times. During ETD procedure, lumen-apposing metal stents (LAMS) were placed in 9 patients, metal coated stents in 2 patients, double pigtail plastic stents in 7 patients, and only a nasal cyst drainage tube in 1 patient. All 19 patients received 12-14 F drainage catheters for drainage during the first percutaneous catheter drainage (PCD) treatment with the mean number of catheters of 1.8±1.2. Double cannulas was subsequently replaced in 3 of them for continuous drainage, and a percutaneous metal coated stent was replaced in 1 patient. The culture results of drainage fluid were 11 cases of gram-negative bacilli and gram-positive cocci, 4 cases of gram-positive cocci, 1 case of gram-positive bacilli, 3 cases of gram-negative bacilli. Among 19 patients, 4 cases had concurrent fungal infections. The mean number of debridement was 3.1±1.8 times, 2 cases of which were treated with endoscopic transluminal necrosectomy combined with percutaneous endoscopic necrosectomy. The mean procedure per patient was 6.1±2.4 times. Bleeding occurred in 1 case (5.3%) after the operation. But the bleeding was successfully stopped after endoscopic hemostasis. No serious complications such as gastrointestinal fistula, perforation or pancreatic fistula occurred. One patient died due to sepsis, and 18 other patients showed significant absorption of IPN after the treatment. None of the 19 patients were transferred to laparotomy.Conclusion:Transgastric combined with percutaneous endoscopic approach is safe and effective for IPN.

Objective:A large single-center, premature acute myocardial infarction (AMI) age (≤45 years) cohort was established to investigate the clinical features and the factors affecting major adverse cardiac events (MACE).Methods:This is a prospective and observational study. 603 patients with a clear diagnosis of AMI admitted to the Tianjin Chest Hospital from March 2015 to December 2017 were continuously selected. All patients were aged ≤45 years old, and a single-center large-sample premature AMI cohort was established. The patient's clinical basic conditions, laboratory indicators, imaging data, coronary angiography and treatment were collected. All patients were followed up for 1 year. MACE events such as cardiac death, recurrent AMI, revascularization, severe heart failure requiring hospitalization and stroke were recorded. Kaplan Meier method was used to draw the survival curve. Cox regression analysis was used to analyze the influence of risk factors, clinical characteristics and intervention methods on the long-term prognosis of MACE events.Results:A total of 603 AMI patients were included, 575 males (95.36%), 28 females (4.64%), and median age 41 (37, 44) years old. There were 422 patients (69.98%) with acute ST segment elevation myocardial infarction (STEMI), 206 patients (48.82%) with anterior myocardial infarction, and 181 patients (30.02%) with non ST segment elevation myocardial infarction (NSTEMI). Smoking was the most common risk factor for premature AMI (77.45%), followed by hyperlipidemia (48.42%) and hypertension (48.09%); smoking was the most common risk factor for male patients (80.35%), and hyperlipidemia was the most common risk factor for female patients (35.71%). 302 (50.08%) patients with premature AMI were treated with symptom onset to first medical contact (SO-to-FMC) ≤12 h; 563 patients (93.37%) had coronary angiography; coronary angiography showed that no significant stenosis, single-vessel disease, double-vessel disease, three-vessel disease, and patients with left main disease were 15(2.66%), 212(37.66%), 153(25.37%), 167(29.66%), 16(2.84%) cases; 318(56.48%) patients with vascular occlusion; The proportion of male combined with left main lesions was lower than that of female group (2.41% vs 12.50%, P=0.026); A total of 45 patients (7.46%) were recorded MACE. The 1-year MACE incidence was lower in the male group than in the female group (6.96% vs 17.86%, P=0.032). Multivariate COX regression analysis: there were 5 indicators that entered the regression model and were statistically significant: female ( HR:4.184; 95% CI:1.583-11.064; P=0.004), SO-to-FMC≤12 h ( HR:0.447; 95% CI:0.224-0.889; P=0.022), left ventricular ejection fraction (LVEF)≤40% ( HR:3.727; 95% CI:1.876-7.405; P<0.001), low-density lipoprotein (LDL) ( HR:1.315; 95% CI:1.041-1.662; P=0.022), homocysteine (Hcy) ( HR:1.011; 95% CI:1.002-1.019; P=0.011) were independent predictor of MACE occurrence in patients with early-onset AMI within 1 year. Conclusions:Smoking is the most common risk factor for young men with AMI. The most common risk factors for young women's AMI is hyperlipidemia, and the proportion of patients with left main artery disease is higher than that of men, but the proportion of patients receiving emergency intervention is lower than that of men, and the long-term prognosis of young women is poor. Early detection and control of these risk factors is a key measure to prevent the onset of AMI.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*