ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Purpose To characterize the clinicopathological features of gastrointestinal mesenchymal tumors(GMTs)resected via endoscopic techniques.Methods A retrospective analysis was conducted on 495 cases of endo-scopically resected GMTs.Clinical information,histomorphological findings,immunohistochemical profiles,and mo-lecular characteristics were reviewed.Results The cohort included 495 patients aged 20-78 years(median:53 years).The majority of tumors were located in the stomach(58.8％)and esophagus(36.8％).Histologically,most tumors consisted of spindle cells,with a minority composed of epithelioid cells;fibrocollagenous or myxoid stroma was occasionally observed.Immunohistochemically,leiomyomas showed diffuse positivity for α-SMA(98.8％)and desmin(99.3％),gastrointestinal stromal tumors(GISTs)expressed CD117(99.4％),DOG1(97.6％),and CD34(97.0％),and schwannomas were positive for S-100(93.7％).The predominant tumor types were leiomyomas(54.1％)and GISTs(33.7％),while the remaining 12.2％comprised other rare types.Various endoscopic resection techniques were employed based on the tumors' anatomical depth,including endoscopic submucosal dissection(ESD,40.5％),submucosal tunneling endoscopic resection(STER,17.1％),endoscopic mucosal resection(EMR,16.5％),endoscopic full-thickness resection(EFTR,13.9％),and endoscopic submucosal excavation(ESE,12.0％).EMR and ESD were primarily used for superficial lesions,while deeper tumors with were more often treated with STER,EFTR,and ESE.The rate of negative resection margins was lower in GISTs(72.2％)and other tumors with indistinct margins,compared to leiomyomas(92.6％)and those with well-defined boundaries.Conclusion Leiomyomas and GISTs are the most common gastrointestinal mesenchymal tumors resected via endoscopy.A variety of resection techniques are applicable depending on tumor location and depth.Accurate pathological diagnosis should be based on HE morphology,supplemented by endoscopic findings,margin status,immunohistochemistry,and necessary molecular tests.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Constructing an efficient and easy-to-operate multigene expression system is currently a crucial part of plant genetic engineering. In this study, a fragment carrying three independent gene expression cassettes and the expression unit of the gene-silencing suppressor protein(RNA silencing suppressor 19 kDa protein, P19) simultaneously was designed and constructed. This fragment was cloned into the commonly used plant expression vector pCAMBIA300, and the plasmid pC1300-TP2-P19 was obtained. Each gene expression cassette consists of different promoters, fusion tags, and terminators. The target gene can be flexibly inserted into the corresponding site through enzymatic digestion and ligation or recombination and fused with different protein tags, which provides great convenience for subsequent detection. The enhanced green fluorescent protein(eGFP) reporter gene was individually constructed into each expression cassette to verify the feasibility of this vector system. The results of tobacco transient expression and laser-confocal microscopy showed that each expression cassette presented independent and normal expression. Meanwhile, the three key enzyme genes in the betanin synthesis pathway, BvCYP76AD, BvDODA1, and DbDOPA5GT, were constructed into the three expression cassettes. The results of tobacco transient expression phenotype, protein immunoblotting(Western blot), and chemical detection of product demonstrated that the three exogenous genes were highly expressed, and the target compound betanin was successfully produced. The above results indicated that the constructed multigene expression system for plants in this study was efficient and reliable and can achieve the co-transformation of multiple plant genes. It can provide a reliable vector platform for the analysis of plant natural product synthesis pathways, functional verification, and plant metabolic engineering.
Nicotiana/metabolism* ; Genetic Vectors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Genetic Engineering/methods* ; Green Fluorescent Proteins/metabolism* ; Gene Expression

OBJECTIVE: To evaluate the analgesic efficacy of ultrasound-guided high fascia iliaca compartment block (HFICB) in managing tourniquet-related pain following total knee arthroplasty (TKA). METHODS: A prospective randomized controlled trial was conducted involving 84 patients with severe knee osteoarthritis or rheumatoid arthritis who underwent unilateral TKA between March 2024 and December 2024. Patients were randomly assigned to two groups ( n=42) using a random number table. In the trial group, ultrasound-guided HFICB was performed preoperatively, with 0.2% ropivacaine injected into the fascia iliaca compartment. No intervention was administered in the control group. Baseline characteristics, including gender, age, surgical side, body mass index, and preoperative visual analogue scale (VAS) scores at rest and during movement, showed no significant difference between the two groups ( P>0.05). In both groups, a tourniquet was applied after osteotomy and before pulsed lavage, and removed after the closure of the first layer of the joint capsule. Postoperative assessments were conducted at 6, 12, 24, and 48 hours, including VAS scores at the tourniquet site (at rest and during movement), Bromage motor block scores, Ramsay sedation scores, and Bruggrmann comfort scale (BCS) scores to evaluate patient comfort. Additionally, the average tramadol consumption and incidence of nausea and vomiting within 48 hours postoperatively were recorded and compared. RESULTS: In the trial group and control group, VAS scores during movement at the tourniquet site significantly improved at all postoperative time points compared to preoperative levels ( P<0.05). VAS scores at rest increased transiently at 6 hours after operation in both groups, and then gradually decreased to the preoperative level. Except that there was no significant difference at 48 hours after operation in the trial group ( P>0.05), there were significant differences at other time points of two groups compared to preoperative score ( P<0.05). Except for VAS score at rest at 6 hours, VAS score during movement at 48 hours, and BCS comfort score at 48 hours ( P>0.05), the trial group showed significantly better outcomes than the control group in terms of VAS score at rest, VAS score during movement, Ramsay sedation scores, and BCS comfort scores at all other time points ( P<0.05). No significant difference was found in Bromage motor block scores between the groups ( P>0.05). Tramadol was used in 3 patients in the trial group and 7 patients in the control group within 48 hours after operation, the dosage was (133.30±14.19) mg and (172.40±22.29) mg, showing significant difference ( P<0.05). Nausea and vomiting occurred in 4 patients (9.5%) in the trial group and 3 patients (7.1%) in the control group, with no significant difference in incidence between groups ( P>0.05). CONCLUSION Ultrasound-guided HFICB provides effective analgesia for tourniquet-related pain following TKA, facilitates early postoperative functional recovery of the knee joint, and may serve as a valuable clinical option for postoperative pain management in TKA patients.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Nerve Block/methods* ; Male ; Female ; Pain, Postoperative/etiology* ; Tourniquets/adverse effects* ; Prospective Studies ; Middle Aged ; Ropivacaine/administration & dosage* ; Aged ; Ultrasonography, Interventional ; Anesthetics, Local/administration & dosage* ; Pain Measurement ; Fascia ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Arthritis, Rheumatoid/surgery*

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

OBJECTIVE: To prepare clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with high expression of hematopoietic supporting factors and evaluate their stem cell characteristics. METHODS: Fetal umbilical cord tissues were collected from healthy postpartum women during full-term cesarean section. Wharton's jelly was mechanically separated and hUC-MSCs were obtained by explant culture method and enzyme digestion method in an animal serum-free culture system with addition of human platelet lysate. The phenotypic characteristics of hUC-MSCs obtained by two methods were detected by flow cytometry. The differences in proliferation ability between the two groups of hUC-MSCs were identified through CCK-8 assay and colony forming unit-fibroblast (CFU-F) assay. The differences in multilineage differentiation potential between the two groups of hUC-MSCs were identified through induction of adipogenic, osteogenic, and chondrogenic differentiation. The mRNA expression levels of hematopoietic supporting factors such as SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in the two groups of hUC-MSCs were identified by real-time fluorescence quantiative PCR(RT-qPCR). RESULTS: The results of flow cytometry showed that hUC-MSCs obtained by the two methods both expressed high levels of CD73, CD90 and CD105, while lowly expressed CD31, CD45 and HLA-DR. The results of CCK-8 and CFU-F assay showed that the proliferation ability of hUC-MSCs obtained by explant culture method was better than those obtained by enzyme digestion method. The results of the triple lineage differentiation experiment showed that there was no significant difference in multilineage differentiation potential between the two grous of hUC-MSCs. The results of RT-qPCR showed that the mRNA expression levels of hematopoietic supporting factors SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in hUC-MSCs obtained by explant cultrue method were higher than those obtained by enzyme digestion method. CONCLUSION Clinical-grade hUC-MSCs with high expression levels of hematopoietic supporting factors were successfully cultured in an animal serum-free culture system.
Humans ; Mesenchymal Stem Cells/metabolism* ; Umbilical Cord/cytology* ; Cell Differentiation ; Female ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Angiopoietin-1/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Stem Cell Factor/metabolism* ; Flow Cytometry ; Pregnancy