ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective To analyze the changes of postoperative pulmonary function in lung transplant recipients. Methods Clinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. Results Postoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity (FVC) to predicted value ratio (FVC%pred), forced expiratory volume in one second (FEV₁) to predicted value ratio (FEV₁%pred), FEV₁/FVC to predicted value ratio (FEV₁/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (D_LCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV₁%pred were gradually increased within postoperative 9 months, and D_LCOc%pred was gradually elevated within postoperative 3 months (all P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV₁%pred≥80% in 41 cases, FEV₁/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 case and FEV₁%pred≤40% in 1 case, respectively. Sixteen recipients had D_LCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (D_LCOc/V_A%pred) ≥80% in 63 cases, D_LCOc%pred≤40% in 4 cases and D_LCOc/V_A%pred≤40% in 1 case, respectively. Postoperative FVC%pred, FEV₁/FVC%pred and D_LCOc%pred in recipients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative D_LCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). Conclusions Pulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.

Progressive multifocal leukoencephalopathy (PML) is a rare and yet serious central nervous system disorder due to JC viral infection.PML occurs predominantly in immunocompromised individuals, including solid organ transplant (SOT) recipients.Clinically, SOT-related PML commonly presents as cognitive and behavioral impairments. Pathologically, PML is characterized by multifocal demyelinating lesions, with neuroimaging technique typically revealing white matter damage in the temporoparietal regions. Clinical diagnosis usually involves integrating clinical manifestations, cranial magnetic resonance imaging, and detection of JC virus in cerebrospinal fluid. Currently, specific medications for PML are lacking, and the treatment mainly relies on supportive care and immunomodulatory strategies. The prognosis of PML remains unfavorable, early diagnosis and enhanced adaptive immune responses are crucial for PML management in SOT recipients.

Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.

Intestinal homeostasis depends on complex interactions between the gut microbiota and host immune system. Emerging evidence indicates that the intestinal microbiota is a key player in autoimmune liver disease (AILD). Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis have been linked to gut dysbiosis. Diverse mechanisms contribute to disturbances in intestinal homeostasis in AILD. Bacterial translocation and molecular mimicry can lead to hepatic inflammation and immune activation. Additionally, the gut and liver are continuously exposed to microbial metabolic products, mediating variable effects on liver immune pathologies. Importantly, microbiota-specific or associated immune responses, either hepatic or systemic, are abnormal in AILD. Comprehensive knowledge about host-microbiota interactions, included but not limited to this review, facilitates novel clinical practice from a microbiome-based perspective. However, many challenges and controversies remain in the microbiota field of AILD, and there is an urgent need for future investigations.

Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.

Objective To analyze the risk factors and clinical prognosis of acute kidney injury (AKI) early after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation or combined heart-lung transplantation were retrospectively analyzed, and they were divided into the AKI group (n=104) and non-AKI group (n=51) according to the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of AKI early after lung transplantation was summarized. The main indexes of recipients were collected. The risk factors of the occurrence of AKI early after lung transplantation were subjected to univariate and multivariate analysis. The clinical prognosis of lung transplant recipients was evaluated and the survival curve was delineated. Results The incidence of AKI early after lung transplantation was 67.1%(104/155), including 47 recipients with stage 1 AKI, 34 recipients with stage2 AKI and 23 recipients with stage 3 AKI, respectively. Sixteen recipients required continuous renal replacement therapy (CRRT) early after lung transplantation. Preoperative complication with diabetes mellitus, preoperative complication with pulmonary hypertension, intraoperative mean arterial pressure (MAP) < 60 mmHg, intraoperative massive blood transfusion, and treatment with excessive therapeutic concentration of tacrolimus (Tac) within postoperative 1 week were the independent risk factors for the occurrence of AKI early after lung transplantation. Up to the end of follow-up, 66 recipients (42.6%) died, including 50 recipients in the AKI group and 16 recipients in the non-AKI group. The cumulative survival rate in the AKI group was significantly lower than that in the non-AKI group (40% vs. 66%, P < 0.05). With the increase of AKI severity, the cumulative survival rate of lung transplant recipients was decreased. Conclusions AKI develops early after lung transplantation with high incidence and poor clinical prognosis. Preoperative complication with diabetes mellitus and pulmonary hypertension, intraoperative MAP < 60 mmHg and massive blood transfusion, and treatment with excessive therapeutic concentration of Tac within postoperative 1 week are the independent risk factors for the occurrence of AKI early after lung transplantation.

Objective To analyze the dynamic changes and the influencing factors of T lymphocyte subsets in recipients with stable graft status within 1 year after lung transplantation. Methods Clinical data of 41 recipients with stable graft status after allogeneic lung transplantation were analyzed. The absolute value and ratio of T lymphocyte subsets in peripheral blood from recipients were measured by flow cytometry before operation, 2 weeks and each month (within 1 year) after operation, respectively. The effects of age, gender, body mass index (BMI), surgical method, incidence of primary graft dysfunction (PGD) after operation, and primary disease upon the absolute values of T lymphocytes were evaluated. Results Within 1 year after lung transplantation, the absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes and CD4⁺/CD8⁺ ratio were changed over time (all P < 0.001). Compared with preoperative values, there was no statistical significance in the absolute values of CD3⁺ and CD3⁺CD4⁺T lymphocytes at 12 months after operation (P=0.659, 0.109), whereas the absolute value of CD3⁺CD8⁺T lymphocytes was increased (P=0.02) and the CD4⁺/CD8⁺ ratio was decreased (P < 0.001). Age, gender, BMI, surgical method and incidence of PGD after operation exerted no significant effect on the dynamic changes of absolute values of CD3⁺CD4⁺ and CD3⁺CD8⁺T lymphocytes (all P > 0.05). Primary disease before lung transplantation exerted no effect on the changes of CD3⁺CD4⁺T lymphocytes, whereas the postoperative absolute value of CD3⁺CD8⁺T lymphocytes was higher in recipients with infectious lung diseases (P < 0.05). Conclusions The absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes in recipients with stable graft status after lung transplantation are relatively low in the early stage after lung transplantation, then gradually restore, and stabilize at 6 months after operation. Dynamic changes are not associated with age, gender, BMI, surgical method and incidence of PGD after operation of recipients.