Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective To observe the changes in the subfoveal choroidal thickness(SFCT)of children and adoles-cents with different refractive states using optical coherence tomography angiography.Methods A total of 171 children and adolescents were followed.They were divided into the lower primary school group(6-8 years old),upper primary school group(9-11 years old),and junior high school group(12-14 years old)according to their age at the time of en-rollment.Dioptric examinations(including best corrected visual acuity,diopter,intraocular pressure,corneal curvature,axial length and SFCT)were performed,data collection was conducted twice in half a year(initial examination and review after half a year),and the eyeball parameters and changes in eyeball parameters after half a year among all groups were compared.Results The axial length and SFCT of subjects had significant differences among all groups(both P＜0.05).In children and adolescents,the axial length gradually lengthened and SFCT gradually thickened with age,while intraocular pressure and corneal curvature were not associated with age(both P＞0.05).In the initial examination and review after half a year,there was no significant difference in intraocular pressure,corneal curvature and SFCT of subjects with differ-ent refractive states in all groups(all P＞0.05),while the axial length of myopic subjects was greater than that of non-my-opic subjects in all groups(all P＜0.05).In the review after half a year,the SFCT of non-myopic subjects in the lower pri-mary school group and upper primary school group was significantly thickened(P＜0.001,P=0.003),while there was no significant difference in SFCT of myopic subjects in all groups compared with the value half a year ago(all P＞0.05).The axial length of all subjects showed a positive correlation with the SFCT in the initial examination and review after half a year(r=0.354,0.228,P＜0.05).Conclusion Myopia affects the increase in SFCT in children and adolescents.

Objective:To systematically review the risk prediction models for cognitive impairment in stroke patients, aiming to provide references for clinical healthcare professionals in selecting or constructing high-quality risk assessment tools.Methods:A computerized search was conducted in PubMed, Embase, Web of Science, OVID, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP to identify studies related to risk prediction models for cognitive impairment in stroke patients. The search was limited to articles published up to August 1, 2023. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability of the included studies using PROBAST.Results:A total of 26 articles were included. The applicability of the studies was generally good, but all studies had some degree of bias risk, mainly arising from unreasonable study designs, inappropriate time intervals between predictor assessment and outcome determination, insufficient sample sizes, unreasonable handling of continuous variables, omission of missing data, lack of reporting of calibration, and overfitting of the models. Meta-analysis results showed that age ( OR=0.05, 95% CI: 0.033-0.057), education level ( OR=-0.13, 95% CI: -0.171 - -0.082), history of diabetes ( OR=2.32, 95% CI: 1.867-2.881), history of hypertension ( OR=0.67, 95% CI: 0.420-0.918), and NIHSS score ( OR=0.40, 95% CI: 0.331-0.469) were factors for cognitive impairment in stroke patients. Conclusions:While various risk prediction models for cognitive impairment in stroke patients exist, they suffer from methodological flaws and high bias risks, with some commonalities and controversies in predictors. Future research should adhere to the principles of transparent reporting of individual prognosis or diagnosis of multivariate prediction models, develop localized prediction models with low bias risk and good applicability, and conduct internal and external validations to demonstrate their applicability and feasibility in clinical practice.

Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.

OBJECTIVE: A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). METHODS: Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. RESULTS: There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). CONCLUSION The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Aged ; Female ; Humans ; Male ; Middle Aged ; Anesthesia, Local/methods* ; Anesthetics, Local/administration & dosage* ; Arthroplasty, Replacement, Knee/methods* ; Bupivacaine/administration & dosage* ; Liposomes ; Osteoarthritis, Knee/surgery* ; Pain Measurement ; Pain, Postoperative/prevention & control* ; Prospective Studies ; Treatment Outcome

Objective:To evaluate the efficacy and safety of budesonide viscous suspension (BVS) in preventing extensive esophageal stenosis after endoscopic submucosal dissection(ESD).Methods:Data of 62 cases of early esophageal neoplasms or precancerous lesions receiving ESD whose postoperative mucosal defects were more than half the circumference of the esophageal lumen at Fujian Provincial Hospital from October 2014 to December 2018 were retrospectively studied. The patients were divided into the BVS group who received BVS therapy (n=24) and the control group who received no intervention (n=38). The incidence of postoperative stenosis, the number of bougie dilation procedures and complications were compared between the two groups. Risk factors for postoperative stricture were analyzed by logistic regression.Results:The incidence of postoperative stenosis [16.7% (4/24) VS 47.3% (18/38), P=0.005], the number of bougie dilation procedures (1.50±0.58 VS 2.70±1.09, P=0.039) in the BVS group were significantly lower than those in the control group. No serious adverse events such as perforation or massive hemorrhage related to BVS were observed in the BVS group. Multivariate logistic regression analysis showed circumferential extension ≥3/4 ( OR=37.970, 95% CI: 6.338-227.482) and non-intervention with BVS( OR=20.962, 95% CI: 3.374-130.243) were the independent risk factors for esophageal stricture after ESD. Conclusion:Administration of BVS is an effective and safe method to reduce the incidence of stenosis and the number of bougie dilation procedures for extensive esophageal stenosis after ESD.

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Objective To explore the role of interleukin (IL)-38 in inhibiting inflammatory bowel disease (IBD) in children and to investigate the potential molecular mechanisms.Methods From January 2014 to October 2017,67 patients with ulcerative colitis (UC) and 115 patients with Crohn's disease (CD)admitted to Wuhan Children's Hospital were recruited,and 40 individuals with normal endoscopic findings were selected as control.Serum levels of IL-38 of IBD patients and healthy control were determined by enzyme-linked immunosorbent assay (ELISA).Immunohistochemical staining (IHC) was used to detect the expression level of IL-38,nuclear factor κB (NF-κB),phosphorylated signal transduction and activator of transcription 3 (p-STAT3),C-reaction protein (CRP) and erythrocyte sedimentation rate (ESR) in the intestinal mucosa of IBD patients and healthy controls.The extent of disease,therapeutic agents and disease activity scores (Mayo score system for UC patients,Crohn's disease activity index (CDAI) for CD patients) were evaluated.IL-38-C57BL/6 transgenic mice model was established,and dextran sulfate sodium was used to induce IBD mice model.The intestinal inflammation levels were compared between the wild type IBD mice and IL-38 transgenic IBD mice.The levels of IL-38,NF-κB and p-STAT3 in intestinal mucosa of mice of different groups were determined by IHC.The ratio of CD4 + IL-17 + T helper (Th) 17 cells in peripheral blood of mice of different groups was detected by flow cytometry.Independent sample t test,chi square test and Pearson correlation were performed for statistical analysis.Results The results of ELISA showed that the serum levels of IL-38 of UC and CD patients were (6.1 ± 1.9) ng/L and (9.8 ±2.1) ng/L,respectively,which both were lower than that of healthy controls ((16.4 ± 2.7) ng/L),and the differences were statistically significant (t =23.107 and 15.853,both P ＜ 0.05).The results of IHC indicated that the levels of IL-38 in the intestinal mucosal tissues of UC and CD patients were 0.04 ± 0.01 and 0.03 ± 0.01,respectively,which were both lower than that of healthy controls (0.18 ± 0.02),and the differences were statistically significant (t =48.186 and 69.443,both P ＜ 0.05).The levels of NF-κB and p-STAT3 of UC and CD patients were 0.150 ± 0.030,0.160 ± 0.040 and 0.130 ±0.030,0.110 ±0.010,which were all higher than those of healthy controls (0.020 ±0.003 and 0.010 ± 0.002),and the differences were statistically significant (tUC =27.273 and 23.078,tCD =23.657 and 62.684;all P ＜ 0.05).The number of patients with disease at active phase,CRP level,ESR and disease activity scores of UC and CD patients with low IL-38 expression were all significantly higher than those of patients with high IL-38 expression (x2UC =11.552,tUC =7.118,8.991 and 7.086;x2CD =5.675,tCD =9.559,9.358 and 11.268;all P ＜ 0.05).The results of Pearson correlation analysis demonstrated that the level of IL-38 in the intestinal mucosal tissue of UC patients was negatively correlated with CRP,ESR and Mayo scores (r =-0.291,-0.672 and-0.639;all P ＜ 0.05).And the level of IL-38 in the intestinal mucosal tissue of CD patients was negatively correlated withCRP,ESRandCDAI (r=-0.559,-0.471 and-0.353;allP＜0.05).The IHC results showed that the levels of NF-κB and p-STAT3 of IL-38 transgenic IBD mice were lower than those of wild type IBD mice (0.14±0.02 vs.0.32 ±0.06,0.12 ±0.02 vs.0.44 ±0.07),and the differences were statistically significant (t =6.971 and 10.767,both P ＜ 0.05).The results of flow cytometry showed that the ratio of CD4 + IL.-17+ Th17 cells in the peripheral blood of IL-38 transgenic IBD mice was lower than that of wild type IBD mice (0.030±0.006 vs.0.280 ±0.050),and the difference was statistically significant (t =12.160,P ＜0.05).Conclusions The expression level of IL-38 significantly decreases in the intestinal mucosal tissues of IBD patients,while the level of NF-κB and p-STAT3 significantly increases.IL-38 may inhibit IBD by regulating NF-κB and p-STAT3 signaling pathway to alleviate intestinal immune reaction.

Objective    To evaluate the strategy of chemoradiotherapy following endoscopic R0 resection for esophageal cancer in M3-T1b stage. Methods    There were 45 esophageal cancer patients with M3-T1b stage with endoscopic R0 resection followed by additional chemoradiotherapy from ECETC (Esophageal Cancer Endoscopic Therapy Consortium) as a trial group with 34 males and 11 females at age of 61.37±7.14 years. There were 90 patients with esophagectomy from Fudan University Shanghai Cancer Center as a control group with 63 males and 27 females at age of 61.04±8.17 years. Propensity score match (1:2) was used to balance the factors: gender, age, position, depth of invasion and lymphovascular invasion (LVI), which may influence the outcomes. Overall survival (OS) rate, relapse free survival (RFS) rate, and local recurrence rate were compared between the two groups. Result    There was no statistical difference (HR=2.66 with 95%CI 0.87 to 8.11, P=0.179) in terms of OS rate between the two groups. One, two and three years overall survival rate of patients in the control group was 93%, 86%, and 84%, respectively. Nobody died in the trial group within 3 years after surgery. The RFS rate between the two groups didn’t significantly differ (HR=1.48, 95% CI 0.66 to 3.33, P=0.389). One, two and three years RFS rate of patients in the contorl group was 87%, 78%, and 76%, respectively, while 97%, 93%, and 73% in the trial group, respectively. The local recurrence rates between the two groups didn’t significantly differ either ( HR=0.53，95%CI 0.13 to 2.18, P=0.314). One, two and three years local recurrence rate of patients in the control group was 5%, 6% and 6%, respectively, while 0%, 0% and 21% in the trial group, respectively. Conclusion    Similar outcomes are found regarding OS, RFS and local recurrence rates between the two groups. The strategy of endoscopic R0 resection followed by additional chemoradiotherapy has prospect for the treatment of esophageal cancer in M3-T1b stage. And this kind of therapy may be provided for those with risk factors or can not tolerate surgery.

Objective To investigate the expressions of a disintegrin and metalloprotease 17 (ADAM17) and epidermal growth factor recepter (EGFR) in human esophageal squamous cell carcinoma (ESC),and to explore their relationship with clinicopathological characteristics.Methods The paraffin specimens in postoperative pathological tissues of 66 ESC patients in the Third People's Hospital of Hefei from January 2013 to December 2017 were selected.Expressions of ADAM17 and EGFR proteins were examined by using immunohistochemistry in 66 cases of ESC tissues and 33 cases of adjacent tissues of the tumors.The relationship of ADAM17 and EGFR with clinicopathological features was analyzed.Kendall method was used to detect the expression correlation of ADAM17 and EGFR.Results The positive rate of ADAM17 protein in ESC tissues was higher than that in the adjacent tissues of the tumors [68.2 ％ (45/66) vs.33.3 ％ (11/33),x2 =10.874,P =0.001].The positive rate of EGFR protein in ESC tissues was higher than that in the adjacent tissues of the tumors [66.7 ％ (44/66) vs.39.4 ％ (13/33),x2 =6.699,P =0.01].The expressions of ADAM17 and EGFR protein were related with ESC pathological TNM staging,infiltration depth,lymph node metastasis (x2 =4.797,4.890,6.089;8.790,8.766,10.154,respectively,all P ＜ 0.05).ADAM17 expression was positively correlated with EGFR protein (r,=0.368,P ＜ 0.05).Conclusions ADAM17 and EGFR are highly expressed in human ESC.Besides,ADAM17 and EGFR have the interaction in the occurrence and development of esophageal cancer.Joint detection may help to determine the degree of metastasis and evaluate prognosis.