ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

Objective To explore the safety and feasibility of mechanical thrombectomy as the first-line endovascular strategy in patients with non-acute symptomatic long-segment internal carotid artery occlusion(ICAO)undergoing revascularization.Methods This study retrospectively and consecutively enrolled non-acute symptomatic long-segment ICAO patients treated in the Department of Neurology,First Hospital of Jilin University,between January 2019 and August 2023,with mechanical thrombectomy as the preferred endovascular modality.Baseline and clinical data were collected,including sex,age,stroke-related risk factors(hypertension,diabetes,dyslipidemia,coronary artery disease,prior stroke,smoking and alcohol use history),admission National Institutes of Health stroke scale(NIHSS)score,pre-operative modified Rankin scale(mRS)score,time from last symptom onset to femoral puncture,time from imaging confirmation to femoral puncture,high-resolution MRI,right-sided ICAO,stump morphology(absent,tapered,flat/blunt,irregular),distal backfilling patterns(above ophthalmic segment,cavernous/clinoid segment,below cavernous segment),pathogenesis(atherosclerosis,dissection),types of anesthesia(local,general),procedure time(time frame from femoral puncture to recanalization or final angiography),site of the original occlusion in successfully recanalized cases,surgical techniques(aspiration+balloon angioplasty,aspiration+balloon angioplasty+stent-retriever thrombectomy,aspiration+balloon angioplasty+stent placement,aspiration+balloon angioplasty+stent-retriever thrombectomy+stent placement),stent placement(yes/no),number of stents implanted,and number of cases with retrieved thrombus,observed indicators.Observed indicators including ratio of technical successful recanalization(immediately post-procedure most severely stenosed site stenosis rate＜50%,expanded thrombolysis in cerebral infarction[eTICI]grade≥2c),intraoperative complications(distal embolization,symptomatic intracranial hemorrhage,arterial perforation)rate,perioperative mortality rate,30-day stroke recurrence,and 90-day mRS score.Compare the baseline data,clinical data and observational indicators of the patients with successful and unsuccessful recanalization.Base on the original occlusion site,successfully recanalized patients were subclassified into isolated extracranial,isolated intracranial,and tandem lesions patients,and their baseline characteristics and observation indicators were compared.Results(1)A total of 65 patients were enrolled(57 men,8 women;age 39-80 years;median 59[52,65]years)in this study.Technical success was achieved in 52cases(80%).Perioperative complications occurred in 4 patients(6.2%),with 3 distal embolization cases(4.6%),1(1.5%)developed symptomatic intracranial hemorrhage,and no arterial perforations were observed.There was no perioperative mortality.The 30-day stroke recurrence rate was 7.7%(5/65).90-day mRS scores ranged from 0 to 4,with a median of 1.0(0.0,1.5).(2)Baseline and clinical characteristics as well as outcome indicators did not differ significantly between patients with successful versus unsuccessful recanalization in the cohort undergoing mechanical thrombectomy for non-acute symptomatic long-segment intracranial carotid artery occlusion(all P＞0.05).(3)Among successfully recanalized patients,17(32.7%)had isolated extracranial lesions,18(34.6%)had isolated intracranial lesions,and 17(32.7%)had tandem lesions.All cases in the extracranial lesions group had original lesion site at the origin of internal carotid artery(C1,17/17).The intracranial group most often had orginal lesion sites at the C4 segment(9/18),whereas tandem lesions predominantly involved C1 plus C4-C5(16/17).Among the three groups,patients with isolated intracranial lesions were younger(57[48,61]years vs.60[52,64],63[58,69]years,P=0.050),and had a lower proportion of right-sided ICAO(4/18 vs.11/17 vs.11/17,P=0.032),while patients with tandem lesions required a greater number of stents(2.0[1.0,2.0]vs.1.0[1.0,1.5],1.0[0.8,2.0],P=0.013).Significant differences were observed in the proportion of patients with retrieved thrombus decreased progressively from patients with isolated extracranial,isolated intracranial to tandem lesions(17/17 vs.17/18 vs.12/17,P=0.024).No significant differences were observed among lesion-site groups with respect to medical history,stump morphology,distal retrograde flow,procedural technique,procedure duration,anesthesia method,or outcome indicators(all P＞0.05).Conclusions This study suggested that utilizing mechanical thrombectomy as the first-line endovascular therapy for non-acute symptomatic long-segment ICAO is safe and feasible.The original occlusive sites of non-acute symptomatic long-segment ICAO predominantly involve the cervical origin and the cavernous segment of the internal carotid artery.The conclusions of this study require further validation.

Objective To explore the safety and feasibility of mechanical thrombectomy as the first-line endovascular strategy in patients with non-acute symptomatic long-segment internal carotid artery occlusion(ICAO)undergoing revascularization.Methods This study retrospectively and consecutively enrolled non-acute symptomatic long-segment ICAO patients treated in the Department of Neurology,First Hospital of Jilin University,between January 2019 and August 2023,with mechanical thrombectomy as the preferred endovascular modality.Baseline and clinical data were collected,including sex,age,stroke-related risk factors(hypertension,diabetes,dyslipidemia,coronary artery disease,prior stroke,smoking and alcohol use history),admission National Institutes of Health stroke scale(NIHSS)score,pre-operative modified Rankin scale(mRS)score,time from last symptom onset to femoral puncture,time from imaging confirmation to femoral puncture,high-resolution MRI,right-sided ICAO,stump morphology(absent,tapered,flat/blunt,irregular),distal backfilling patterns(above ophthalmic segment,cavernous/clinoid segment,below cavernous segment),pathogenesis(atherosclerosis,dissection),types of anesthesia(local,general),procedure time(time frame from femoral puncture to recanalization or final angiography),site of the original occlusion in successfully recanalized cases,surgical techniques(aspiration+balloon angioplasty,aspiration+balloon angioplasty+stent-retriever thrombectomy,aspiration+balloon angioplasty+stent placement,aspiration+balloon angioplasty+stent-retriever thrombectomy+stent placement),stent placement(yes/no),number of stents implanted,and number of cases with retrieved thrombus,observed indicators.Observed indicators including ratio of technical successful recanalization(immediately post-procedure most severely stenosed site stenosis rate＜50%,expanded thrombolysis in cerebral infarction[eTICI]grade≥2c),intraoperative complications(distal embolization,symptomatic intracranial hemorrhage,arterial perforation)rate,perioperative mortality rate,30-day stroke recurrence,and 90-day mRS score.Compare the baseline data,clinical data and observational indicators of the patients with successful and unsuccessful recanalization.Base on the original occlusion site,successfully recanalized patients were subclassified into isolated extracranial,isolated intracranial,and tandem lesions patients,and their baseline characteristics and observation indicators were compared.Results(1)A total of 65 patients were enrolled(57 men,8 women;age 39-80 years;median 59[52,65]years)in this study.Technical success was achieved in 52cases(80%).Perioperative complications occurred in 4 patients(6.2%),with 3 distal embolization cases(4.6%),1(1.5%)developed symptomatic intracranial hemorrhage,and no arterial perforations were observed.There was no perioperative mortality.The 30-day stroke recurrence rate was 7.7%(5/65).90-day mRS scores ranged from 0 to 4,with a median of 1.0(0.0,1.5).(2)Baseline and clinical characteristics as well as outcome indicators did not differ significantly between patients with successful versus unsuccessful recanalization in the cohort undergoing mechanical thrombectomy for non-acute symptomatic long-segment intracranial carotid artery occlusion(all P＞0.05).(3)Among successfully recanalized patients,17(32.7%)had isolated extracranial lesions,18(34.6%)had isolated intracranial lesions,and 17(32.7%)had tandem lesions.All cases in the extracranial lesions group had original lesion site at the origin of internal carotid artery(C1,17/17).The intracranial group most often had orginal lesion sites at the C4 segment(9/18),whereas tandem lesions predominantly involved C1 plus C4-C5(16/17).Among the three groups,patients with isolated intracranial lesions were younger(57[48,61]years vs.60[52,64],63[58,69]years,P=0.050),and had a lower proportion of right-sided ICAO(4/18 vs.11/17 vs.11/17,P=0.032),while patients with tandem lesions required a greater number of stents(2.0[1.0,2.0]vs.1.0[1.0,1.5],1.0[0.8,2.0],P=0.013).Significant differences were observed in the proportion of patients with retrieved thrombus decreased progressively from patients with isolated extracranial,isolated intracranial to tandem lesions(17/17 vs.17/18 vs.12/17,P=0.024).No significant differences were observed among lesion-site groups with respect to medical history,stump morphology,distal retrograde flow,procedural technique,procedure duration,anesthesia method,or outcome indicators(all P＞0.05).Conclusions This study suggested that utilizing mechanical thrombectomy as the first-line endovascular therapy for non-acute symptomatic long-segment ICAO is safe and feasible.The original occlusive sites of non-acute symptomatic long-segment ICAO predominantly involve the cervical origin and the cavernous segment of the internal carotid artery.The conclusions of this study require further validation.

Epidermal growth factor receptor 2 (HER2) is an oncogene involved in tumour genesis and progression. It is expressed in 7% of patients with colorectal cancer (CRC) and is associated with drug resistance of epidermal growth factor receptor monoclonal antibodies. With the emergence of the therapeutic dilemma of CRC and the survival benefits of targeting HER2 for patients with breast cancer and gastric cancer, the significance of HER2 in CRC and the prognostic value of anti-HER2 therapy have been widely concerned, clinical researches on HER2-positive CRC have been continuously carried out. Currently, the diagnostic criteria for HER2 positive CRC have gradually been unified. HER2-targeting therapies such as monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug coupling and HER2-related immunotherapy alone or in combination have shown good efficacy and brought significant survival benefits for HER2 positive CRC. This paper reviews the research progress of HER2 in CRC.

Objective To explore the safety and efficacy of endovascular treatment(EVT)in patients with acute posterior circulation ischemic stroke over 24 hours from onset.Methods This retrospective study retrospectively analyzed patients with acute posterior circulation ischemic stroke who received EVT in the Department of Neurology,First Hospital of Jilin University from June 2018 to June 2023.The patient's gender,age and other related demographic information were collected.The related examination results of patients were collected,including admission rapid blood glucose,admission systolic blood pressure,admission diastolic blood pressure.The related risk factors of stroke of patients were collected,including previous transient ischemic attack,hypertension,diabetes,atrial fibrillation,and history of drinking,smoking history,etc.;other related indicators were collected,including intravenous thrombolysis,tandem lesions,awakening stroke,baseline National Institutes of Health stroke scale(NIHSS)score,and baseline posterior circulation Alberta stroke program early CT score(pc-ASPECTS),collateral circulation grade of American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR),onset to EVT puncture time,the trial of org 10172 in acute stroke treatment(TOAST)classification and outcome indicators(efficacy indicators included 90 days Modified Rankin scale[mRS]score≤3 after EVT,successful recanalization[extended cerebral infarction thrombolytic recanalization class 2b-3];security indexes included symptomatic intracranial hemorrhage[sICH]within 24 h after EVT and 90 d mortality after EVT).According to the symptom onset to EVT puncture time,the patients were divided into two groups:≤24h group and＞24h group.The patients with onset time＞24 h and those with onset time≤24 h were matched at a ratio of 1:1 by propensity score matching(PSM).All patients were divided into poor prognosis group(mRS score＞3)and good prognosis group(mRS score ≤ 3)according to mRS score at 90 days after EVT.Using univariate and multivariate Logistic regression was used to analyze the effect of onset time on clinical outcomes at 90 days after EVT.Results A total of 366 patients were enrolled in this study,including 284 males and 82 females.The median age was 61(55,68)years old,ranging from 25 to 91 years old.Before PSM,the＞24h group had lower prevalence of atrial fibrillation(2.02％[2/99]vs.9.74％[26/267],P=0.025)and lower baseline NIHSS score(10.0[5.0,19.0]vs.14.0[10.0,35.0],P＜0.01)and higher ASTIN/SIR collateral grade(P=0.018).After PSM,we did not find statistical difference between the two groups in baseline characteristics except for the onset to EVT puncture time.Before and after PSM,there was no significant difference in efficacy and safety between the onset time＞24 h group and the onset time ≤24h group.Univariate binary Logistic regression analysis showed that hypertension(OR,0.613,95％CI 0.391-0.942,P=0.025),intravenous thrombolysis(OR,3.235,95％CI 1.316-9.237,P=0.010),baseline NIHSS score(OR,0.975,95％CI 0.957-0.988,P＜0.01),baseline pc-ASPECTS(OR,1.281,95％CI 1.101-1.482,P=0.001)and sICH within 24 h after EVT(OR,0.070,95％CI 0.000-0.330,P＜0.01)were significantly correlated with prognosis.Gender,age,hypertension,baseline NIHSS score,intravenous thrombolysis,baseline pc-ASPECTS,ASTIN/SIR collateral grade,onset time＞24 h and sICH within 24 h after EVT were included in the multivariate binary Logistic regression analysis.The multivariate binary Logistic regression analysis showed that the onset time＞24 h was not associated with poor prognosis 90 d after EVT(aOR,1.635,95％CI 0.936-2.893,P=0.087).Conclusion EVT for acute posterior circulation ischemic stroke more than 24 hours after onset is feasible under strict imaging screening,and its safety and efficacy are similar to those in patients with onset under 24 hours.

Objective:To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h.Methods:In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events.Results:Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading ( P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95% CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95% CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion:For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

Objective:To observe the effect of thoracic infusion of pseudomonas aeruginosa injection in malignant pleural effusion. Methods:A total of 90 patients with malignant pleural effusion were randomly divided into treatment group (31 cases),control group A (29 cases) and control group B(30 cases). Treatment group was treated with pseudomonas aeruginosa through intrathoracic infusion. Control group A and B were respectively treated with cisplatin and interleukin-2 through intrathoracic infusion. The clinical efficacy and adverse reaction were compared among the three groups. Results:The total effective rate of treatment group was 80.6%,the total effective rates of the control group A and B were 51.7%and 56.7%respectively.Compared with that of contral groups, the total effective rate of treatment group was higher, and the differences were statistically significant (P<0.05). The incidence of serious side effects and toxicity was lower in treatment group than in control groups. Conclusion:The effect of thoracic infusion of pseudomonas aeruginosa injection for malignant pleural effusion is significant, and the adverse reaction is mild. Thus it is worth to be promoted clinically.