Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Objective:To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy.Methods:A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors.Results:The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR=18.00, 95% CI 1.56-207.45, P=0.020) and bone marrow suppression ( OR=18.00, 95% CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions:PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Objective:To observe the effect of electroacupuncture(EA)combined with repetitive transcranial magnetic stimulation(rTMS)on limb dysfunction in ischemic stroke patients. Methods:A total of 63 stroke patients were divided into an observation group and a control group using the random number table method.Thirty-one patients in the control group were treated with routine Western medicine combined with rTMS;32 patients in the observation group were treated with EA in addition to the intervention in the control group.The duration of treatment was 3 months.The National Institutes of Health stroke scale(NIHSS),the Fugl-Meyer assessment(FMA),the modified Barthel index(MBI),and the motor evoked potential(MEP)latency of transcranial magnetic stimulation were observed before and after treatment in both groups. Results:Two cases withdrew from the observation group and 1 case withdrew from the control group.After treatment,the NIHSS score in both groups was lower than that before treatment,the FMA and MBI scores were higher than those before treatment,and the latency period of MEP was shorter than that before treatment,and the differences were statistically significant(P<0.05).After treatment,the NIHSS,FMA,and MBI scores and MEP latency period of the observation group improved more than those of the control group,and the differences between the groups were statistically significant(P<0.05). Conclusion:EA combined with rTMS can improve the motor function of limbs in ischemic stroke patients and improve their self-care ability.The mechanism may be related to increasing the excitability of the motor cortex and improving the electrophysiological function of the central nervous system.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To explore the morphological characteristics of the pectoralis major muscle and the anatomical relationship of adjacent structures .Methods:A total of 156 patients undergoing thyroid surgery at the First Hospital of Anhui University of Science & Technology and the First Affiliated Hospital of University of Science and Technology of China from Dec 2020 to Sep 2022 were includeed. Those adopting routine endoscopic thyroidectomy by gasless unilateral axillary approach were assigned to group A,and searching for the sternocleidomastoid muscle through the pectoralis major muscle gap on this basis to group B.Results:Among the 78 patients in group B, a total of 71 (91%) cases were found to have a typical sternocleidomastoid muscle gap, and in 7 (9%) cases were not found. The morphology phenotypes of the gap between the clavicular part and thoracic ribs part of the pectoralis major muscle was found in 3 types: obvious separation type (typeⅠ), inconspicuous separation-partially overlapped type (typeⅡa), and inconspicuous separation-completely anastomosed type (type Ⅱb). The mean duration of surgery in group B was less (105±15) min than that in group A (156±27) min ( t=14.523, P<0.01); postoperative one day drainage in group B was less (49±6) ml than that in group A (51±6) ml ( t=2.273, P=0.024). There was no statistically significant difference in intraoperative bleeding, postoperative hospital stay and complication rate between the two groups ( t=0.557, P=0.578; t=0.134, P=0.894; χ2=1.844, P=0.174). Conclusion:The search for the sternocleidomastoid muscle through the pectoralis major muscle gap in the endoscopic thyroidectomy by gasless unilateral axillary approach can shorten the duration of surgery and improve the efficiency of surgery.

Objective     To investigate the perioperative clinical effects and follow-up results of minimally invasive coronary artery bypass grafting (MICS CABG) versus conventional coronary artery bypass grafting (CABG) in thoracotomy. Methods     The patients who received off-pump CABG in Beijing Anzhen Hospital from January 2017 to October 2021 were collected. Among them, the patients receiving MICS CABG performed by the same surgeon were divided into a minimally invasive group, and the patients receiving median thoracotomy were into a conventional group. By propensity score matching, preoperative data were balanced. Perioperative and postoperative follow-up data of the two groups were compared. Results     A total of 890 patients were collected. There were 211 males and 28 females, aged 60.54±9.40 years in the minimally invasive group, and 487 males and 164 females, aged 62.31±8.64 years in the conventional group. After propensity score matching, there were 239 patients in each group. Compared with the conventional group, patients in the minimally invasive group had longer operation time, shorter drainage duration, less drainage volume on the first postoperative day, shorter postoperative hospital stay, and lower rate of positive inotropenic drugs use, while there was no statistical difference in the mean number of bypass grafts, ICU stay, ventilator-assisted time, blood transfusion rate or perioperative complications (P>0.05). During the median follow-up of 2.25 years, there was no statistical difference in major adverse cardiovascular and cerebrovascular events, including all-cause death, stroke or revascularization between the two groups (P>0.05). Conclusion    Reasonable clinical strategies can ensure perioperative and mid-term surgical outcomes of MICS CABG not inferior to conventional CABG. In addition, MICS CABG has the advantages in terms of postoperative hospital stay, postoperative drainage volume, and rate of positive inotropic drugs use.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Objective:The perioperative and early follow-up data of the simultaneous hybrid CAS+ OPCABG and sequential CAS+ OPCABG were compared to evaluate the safety and efficacy of the simultaneous CAS+ OPCABG.Methods:A total of 26 patients with coronary heart disease complicated with carotid artery stenosis received CAS plus OPCABG hybrid surgery in our hospital from January 2020 to July 2021, among which 12 patients received simultaneous CAS+ OPCABG and 14 patients received staged sequential CAS+ OPCABG.The perioperative and postoperative follow-up data of 3 months were compared and analyzed.Results:There were no significant differences in the operation time, drainage on the first day after surgery, ventilator assisted time and ICU time between the two groups.The amount of intraoperative blood loss in the simultaneous group was more than that in the staged group, but no secondary thoracotomy occurred in both groups. The number of days in hospital after operation was significantly less in the simultaneous group. There was 1 case of perioperative cerebral infarction and 1 case of myocardial infarction in the staged group, but there was no statistical difference between the two groups. There was no new cerebral infarction in the two groups, carotid artery ultrasound stent was unobstructed, and there was no statistical difference in cardiac function grading and left ventricular ejection fraction 3 months after operation.Conclusion:Simultaneous CAS+ OPCABG surgery is safe and feasible, it is recommended as the first choice especially for patients with severe myocardial ischemiaor severe left main artery disease caused.How to reduce the risk of bleeding and alleviat carotid sinus reflex are major issues that need to be concerned.

Objective     To compare the mid- and long-term efficacy of minimally invasive coronary artery bypass grafting (MICS) versus conventional coronary artery bypass grafting (CABG). Methods     This study analyzed 679 patients with coronary heart disease treated in the Minimally Invasive Heart Center of Beijing Anzhen Hospital from 2015 to 2019, including 532 males and 147 females with an average age of 61.16 years. A total of 281 patients underwent MICS (a MICS group) and 398 patients underwent conventional CABG (a CABG group). The clinical data of the patients in the two groups were analyzed. Results    The average operation time was longer (P<0.001), the total hospital stay was shorter (P<0.001), and the amount of drainage 24 h after the operation was less (P=0.029) in the MICS group. There was no statistical difference in the incidence of perioperative complications between the two groups. The median follow-up time was 2.68 years. The follow-up results showed that the total incidence of cumulative main adverse cardiovascular and cerebrovascular events in the CABG group was higher at 2 years (6.2% vs. 3.8%) and 4 years (9.3% vs. 7.6%), but the difference was not statistically significant (P>0.05). There was no statistical difference in 2- or 4-year all-cause death between the two groups (3.5% vs. 2.8%, 5.6% vs. 2.8%, P>0.05). At the same time, there was no statistical difference in the incidence of myocardial infarction, stroke or revascularization between the two groups (P>0.05). Conclusion    Compared with conventional CABG, MICS can achieve satisfactory mid- and long-term outcomes.