ObjectiveTo investigate the mechanisms by which Liuwei Buqi prescription （LWBQ） regulates alveolar macrophage efferocytosis and improves inflammatory responses in rats with chronic obstructive pulmonary disease （COPD） characterized by lung-kidney Qi deficiency based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/macrophage receptor with collagenous structure （MARCO） pathway. MethodsSuccessfully modeled rats were randomly divided into a model group， low-dose LWBQ group （LWBQ-L， 2.25 g·kg^-1·d^-1）， medium-dose LWBQ group （LWBQ-M， 4.5 g·kg^-1·d^-1）， high-dose LWBQ group （LWBQ-H， 9 g·kg^-1·d^-1）， and aminophylline group （AMIN， 50 mg·kg^-1·d^-1）， with 8 rats in each group. Another 8 healthy rats were included as the blank group. Except for the blank group， rats in the remaining groups were subjected to smoke exposure combined with forced swimming， intratracheal lipopolysaccharide （LPS） instillation， and subcutaneous hydrocortisone injection to establish a COPD model with lung-kidney Qi deficiency. After successful modeling， rats were administered different doses of LWBQ or AMIN by gavage. Body weight， fur condition， and oral secretions were observed. Pulmonary function was measured using an animal lung function analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interferon-γ （IFN-γ）， interleukin-6 （IL-6）， interleukin-1 （IL-1）， and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） and serum （SER）. Hematoxylin-eosin （HE） staining was used to examine pathological changes in lung tissue. Giemsa staining was performed to detect eosinophils， basophils， and neutrophils in BALF. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was used to detect apoptosis in lung tissue. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA expression levels of efferocytosis-related proteins growth arrest-specific gene 6 （GAS6）， milk fat globule-epidermal growth factor 8 （MFG-E8）， and pathway-related proteins Nrf2 and MARCO in lung tissue. ResultsCompared with the blank group， the model group showed reduced food intake， nasal and oral secretions with sputum， and decreased body weight （P<0.01）， decreased peak expiratory flow （PEF） （P<0.01）， increased forced vital capacity （FVC） （P<0.01）， and decreased forced expiratory volume in 0.3 s/forced vital capacity ［FEV0.3/FVC （%）］ （P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were increased （P<0.01）. Lung tissue exhibited structural destruction， hyperplasia， inflammatory exudation， increased apoptotic cells， and increased mean optical density （P<0.01）. The protein and mRNA expression levels of GAS6， MFG-E8， and MARCO， as well as Nrf2 mRNA expression， were increased （P<0.01）. Compared with the model group， the LWBQ groups showed increased food intake， reduced nasal and oral secretions with sputum， and increased body weight （P<0.05， P<0.01）. PEF was increased （P<0.01）. FVC was increased in rats treated with low- and medium-dose LWBQ （P<0.01）， and FEV0.3/FVC （%） was increased in rats treated with medium- and high-dose LWBQ （P<0.05， P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were decreased （P<0.01）. Lung tissue structure was relatively intact， with improvement in hyperplasia and inflammatory exudation. The number of apoptotic cells in lung tissue was reduced， and mean optical density was decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of efferocytosis-related proteins GAS6 and MFG-E8 and pathway-related proteins Nrf2 and MARCO were increased （P<0.01）. ConclusionLWBQ can alleviate pulmonary and systemic inflammation， improve lung function， and reduce lung tissue damage in rats with COPD characterized by lung-kidney Qi deficiency. The mechanism may be related to enhancement of alveolar macrophage efferocytosis through regulation of the Nrf2/MARCO pathway.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

Objective:To investigate the safety of the use of the intermediate catheter in the endovascular treatment (EVT) of patients with acute anterior circulation large vessel occlusive stroke and its impact on the outcomes.Methods:From May 2015 to September 2018, patients with anterior circulation large vessel occlusive stroke received EVT in Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to whether intermediate catheter was used during the procedure, they were divided into intermediate catheter group and non-intermediate catheter group. The demographics, clinical data and procedure related information were collected. The outcome evaluation indicators included secondary embolization, symptomatic intracranial hemorrhage, clinical outcome and death at 90 d after onset. A good outcome was defined as the modified Rankin Scale score of 0-2. Multivariate logistic regression analysis was used to determine the independent predictor of clinical outcome. Results:A total of 195 patients with anterior circulation large artery occlusive stroke received EVT were enrolled, including 161 in the intermediate catheter group and 34 in the non-intermediate catheter group. There were no significant differences in demographics and clinical characteristics between the intermediate catheter group and the non-intermediate catheter group. In terms of procedure related information, the number of mechanical thrombectomy passes in the intermediate catheter group was significantly decreased (2 [1-3] times vs. 2.5 [1.75-4] times; Z=2.218, P=0.017), the recanalization rate of one-pass thrombectomy was significantly higher (38.5% vs. 20.6%; χ2=3.943, P=0.047), and the rate of thrombus escape and secondary embolism was significantly lower (19.3% vs. 35.3%; χ2=4.202, P=0.041). In terms of clinical outcome, there were no significant differences in the incidence of symptomatic intracranial hemorrhage, mortality and good outcome at 90 d between the intermediate catheter group and the non-intermediate catheter group. Multivariate logistic regression analysis showed that the use of intermediate catheter was an independent predictor of good outcome at 90 d (odds ratio 0.430, 95% confidence interval 0.196-0.947; P=0.036). Conclusion:In EVT of patients with acute anterior circulation large vessel occlusive stroke, the use of intermediate catheter can reduce the number of mechanical thrombectomy passes, improve recanalization rate of one-pass thrombectomy, reduce the rate of thrombus escape and second embolization, and then improve the outcome of patients.

Objective:To analyze the correlation of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)levels with the severity of coronary heart disease in elderly patients.Methods:Clinical data of 200 elderly patients with coronary heart disease in the hospital from January 2017 to July 2019 were retrospectively collected.Data of 80 healthy elderly patients undergoing regular physical examinations in our hospital during the same period were collected and used as the healthy control group.All patients received laboratory tests using relevant parameters and coronary angiography on admission, with complete records of examination results for analysis.Based on SYNTAX scores from angiography of coronary artery lesions, all 200 elderly patients with coronary heart disease were further divided into a low-risk lesion subgroup, an intermediate-risk lesion subgroup and a high-risk lesion subgroup.The correlation of serum Lp-PLA2 and NLRP3 levels with the severity of coronary lesions was analyzed in elderly patients with coronary heart disease.Results:The mean SYNTAX score was 27.6±10.1.There were 60 cases with low-risk lesions, 68 cases with intermediate-risk lesions and 72 cases with high-risk lesions, accounting for 30.0%, 34.0% and 36.0%, respectively.The control group had the lowest serum levels of Lp-PLA2 and NLRP3, followed by the low-risk lesion, intermediate-risk lesion and high-risk lesion subgroups( F=305.026, 9.173 and 582.029, all P<0.001). Bivariate Pearson correlation analysis showed that serum levels of Lp-PLA2 and NLRP3 were positively correlated to the Syntax score in elderly patients with coronary heart disease( r=0.545 and 0.689, all P<0.001). Conclusions:Serum levels of Lp-PLA2 and NLRP3 are correlated to the severity of coronary artery disease in elderly patients with coronary heart disease.Overexpression of these two markers may indicate growing severity of coronary artery disease.Testing for serum Lp-PLA2 and NLRP3 levels in elderly patients with coronary heart disease can be considered to evaluate coronary lesions and treatment options in the future.

Objective:To examine potential predisposing risk factors for coronary heart disease(CHD)in elderly patients and the correlation between serum uric acid levels and the predisposing risk factors in elderly patients with CHD.Methods:Clinical data of 200 elderly inpatients with CHD(CHD group)and 150 elderly outpatients without CHD(control group)at our hospital from January 2017 to January 2019 were retrospectively analyzed.Peripheral venous blood was collected from patients immediately after admission, and serum uric acid levels were measured.Baseline information of patients was recorded.Potential predisposing risk factors of CHD were identified by single-factor and multiple-factor analysis, and serum uric acid levels were compared against predisposing risk factors.The correlation between serum uric acid levels and predisposing risk factors in elderly patients with CHD was analyzed.Results:According to preliminary single-factor analysis, smoking, diabetes mellitus, low high-density lipoprotein cholesterol(HDL-C)hypolipidemia, family history of CHD and glomerular filtration rate seemed to be predisposing risk factors for elderly patients with CHD( χ2=6.739, 15.655, 6.331, 9.615, 23.279, P<0.05). Multiple-factor analysis showed that smoking, diabetes mellitus, low HDL-C hypolipidemia, family history of CHD and glomerular filtration rate were predisposing risk factors for elderly patients with CHD( OR=1.777, 2.381, 1.883, 1.967, 3.205, all P<0.05). Serum uric acid levels in elderly CHD patients with smoking, diabetes mellitus, low HDL-C hypolipidemia, family history of CHD or glomerular filtration rate<100 ml/min were higher than in patients without any of those conditions, and the difference was statistically significant( t=8.017, 5.907, 8.509, 7.164, 13.839, P<0.001). Spearman correlation analysis showed that serum uric acid levels were positively correlated with risk factors such as smoking, diabetes mellitus, and family history of CHD in elderly patients with CHD( r=0.409, 0.422, 0.422, all P<0.001), and were negatively correlated with low HDL-C hypolipidemia and glomerular filtration rate( r=-0.428 and -0.481, all P<0.001). Conclusions:High level serum uric acid is closely related to many CHD risk factors such as smoking and diabetes mellitus and may be an independent risk factor for the onset of CHD.

Objective: To compare the effects of modified Thrombolysis in Cerebral Infarction score (mTICI) 2b and mTICI 3 reperfusion on lesions′ changes and prognosis in patients who underwent endovascular therapy within six hours after onset. Methods: A retrospective analysis was conducted on 94 patients with acute large intracranial artery occlusion of the anterior circulation who achieved reperfusion sucesssfully by endovascular therapy within 6 hours after onset in the Department of Neurology, Nanjing First Hospital from October 2016 to March 2019. The effects of mTICI 2b and mTICI 3 reperfusion on lesions′ changes and prognosis of patients were compared. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days; the secondary endpoints were the early neurological deficit score, the mortality at 90 days, the volume of infarction at 24 hours, the changes in infarct volume for 24 hours and the rate of symptomatic intracerebral hemorrhage (sICH) , reocclusion and hemorrhagic transformation. Results: In all patients, 35 cases received mTICI 2b reperfusion and 59 cases received mTICI 3 reperfusion. Compared with mTICI 2b group (10.00 (3.00, 16.00)), the early neurological deficit score at seven days of mTICI 3 group (6.00 (1.00,11.50)) was lower (Z=-2.004, P=0.045) . However, there were no statistically significant differences in mRS score at 90 days, early neurological deficit score at 24 hours and 3 days, mortality at 90 days, volume of infarction at 24 hours, the changes in infarct volume for 24 hours, and the rate of sICH, reocclusion, and hemorrhagic transformation between the two groups. Conclusion For patients with large intracranial artery occlusion of the anterior circulation within six hours after onset, achieving mTICI 3 reperfusion after endovascular therapy can improve the early neurological function more effectively, but the effects on 90-day functional outcome are similar to that of mTICI 2b reperfusion.

Objective To investigate the effect and safety of intravenous thrombolytic therapy in the endovascular treatment of acute anterior circulation vascular occlusive stroke.Methods The clinical data of 226 patients with acute anterior circulation vascular occlusive stroke who underwent endovascular treatment in Nanjing First Hospital,Nanjing Medical University from May 2015 to May 2018 were retrospectively collected.According to whether or not intravenous thrombolysis was performed,the patients were classified into simple thrombectomy group (n=112) and bridging treatment group (n=114).The modified Thrombolysis in Cerebral Infarction Score (mTICI) was used to evaluate the vascular opening effect,and the blood vessel recanalization time,mTICI,the symptomatic intracranial hemorrhage rate,and the modified Rankin Scale (mRS) score at 90 days after surgery were evaluated.Results There were no statistically significant differences in gender,age,past history and National Institute of Health Stroke Scale score between the two groups (P＞0.05).There was no statistically significant difference in door-to-recanalization time between the two groups (P＞0.05).Excluding the patients with post-wake stroke and unexplained onset time,the simple thrombectomy group (n=63) and the bridging treatment group (n=1 11) showed statistically significant differences in onset-to-door time ((235.04± 182.64) min vs (102.48±60.51) min,t=7.01,P＜0.01)and onset-to-recanalization time ((405.31 ± 148.89) min vs (337.31 ± 117.65) min,t=3.32,P=0.01).The difference in number of thrombectomy between the simple thrombolysis group (2.55± 1.52) and the bridging treatment group (2.11± 1.48) was statistically significant (t=2.246,P=0.026).The total reperfusion (mTICI 2b/3) rate was 89.8％ (203/226),88.4％ (99/112) in the simple thrombectomy group and 91.2％ (104/114) in the bridging treatment group,with no statistically significant difference between the two groups (P＞0.05).The differences in symptomatic intracranial hemorrhage rate (8.93％ (10/112) vs 11.4％ (13/114)),mortality rate (12.5％ (12/112) vs 16.7％ (19/114)) and 90-day good functional outcome (mRS score 0-2;54.5％ (61/112) vs 55.8％ (63/114)) between the two groups were not statistically significant (P＞0.05).Conclusions In patients with acute anterior circulation vascular occlusive stroke undergoing endovascular treatment,intravenous thrombolysis can reduce the number of thrombectomy,not increase the door-to-recanalization time,the risk of symptomatic intracranial hemorrhage and mortality,and has similar good functional outcome as the simple thrombeetomy group.Therefore,intravenous thrombolysis is safe and effective for endovascular treatment of acute anterior circulation large vessel occlusive stroke.

Immunoproteasome is associated with various diseases such as hematologic malignancies, inflammatory, autoimmune and central nervous system diseases, and over expression of immunoproteasome is observed in all of these diseases. Immunoproteasome inhibitors can reduce the expression of immunoproteasome by inhibiting the production of related cell-inducing factors and the activity of T lymphocyte for treating related diseases. In order to achieve good efficacy and reduce the toxic effects, key for development of selective immunoproteasome inhibitors is the high selectivity and potent activity of the three active subunits of the proteasome. This review summarizes the structure and functions of immunoproteasome and the associated diseases. Besides, structure, activity and status of selective immunoproteasome inhibitors are also been highlighted.

Objective Due to the problem of individual matching, exclusivity and loose with pure mechanical fixation for artificial hemi-knee joints made by traditional method, a new manufacturing process based on rapid prototyping technique and custom-made concept is presented.MethodsRapid prototyping was processed to rapidly and accurately shape the prototype of an artificial implant almost with the same shape as the hemi-knee joint of the patient, and the process based on Titanium alloy centrifugal casting technology and biomaterial sintering molding technology was used to fabricate the artificial hemi-knee joint and bioactive proximal tibia artificial bone, respectively.Results and ConclusionThe custom-made knee joint prosthesis has been fabricated and put into clinical use successfully. In comparison with the traditional implants, this system can realize the well matching movement between the artificial hemi-knee joint and its opposite. Meanwhile,the design of functional holes and tibial nails realizes the combination of biological fixation with mechanical fixation for the artificial implant,and the use of bioactive artificial bone promotes bone growth and minimizes the exclusive reaction.