Objective To investigate the role and mechanism of epithelial-mesenchymal transition(EMT)in a rat model of bronchopulmonary dysplasia(BPD).Methods The experiment consisted of two parts.(1)Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group,with 24 rats in each group.The hyperoxia group was exposed to 85%oxygen to establish a BPD model,while the normoxia group was kept in room air at normal pressure.Lung tissue samples were collected on days 1,4,7,and 14 of the experiment.(2)Rat type II alveolar epithelial cells(RLE-6TN)were randomly divided into a normoxia group(cultured in air)and a hyperoxia group(cultured in 95%oxygen),and cell samples were collected 12,24,and 48 hours after hyperoxia exposure.Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs,and immunofluorescence was used to detect the co-localization of surfactant protein C(SPC)and α-smooth muscle actin(α-SMA)in preterm rat lung tissue and RLE-6TN cells.Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells.Results(1)Compared with the normoxia group,the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure.Co-localization of SPC and α-SMA was observed in lung tissue,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group.In the hyperoxia group,the mRNA and protein levels of TGF-β1,α-SMA,and N-cadherin were increased,while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group(P<0.05).(2)SPC and α-SMA was observed in RLE-6TN cells,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group.Compared to the normoxia group,the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased,while the mRNA and protein levels of TGF-β1,α-SMA,and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure(P<0.05).Conclusions EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD,leading to simplified alveolar structure and abnormal development,and is involved in the development of BPD.

Objective To explore the effectiveness and safety of percutaneous coronary artery shock wave balloon angioplasty(IVL)under the guidance of intravascular ultrasound(IVUS)for the treatment of severe calcification lesions in the left main artery(LM).Methods A total of 26 patients with severe LM(mouth,body,bifurcation)calcification admitted to Jiangnan University Affiliated Hospital from October 2022 to April 2024 were included,with an average age of 72.0(61.8,75.4)years.Under the guidance of IVUS,IVL was used for pre-treatment of calcified lesions,followed by percutaneous coronary intervention(PCI)with stent/drug balloon implantation.All patients were evaluated using IVUS before and after the use of IVL and after PCI.And compare the IVUS intracavity related data before and after treatment[plaque burden(PB)、minimum lumen area(MLA)、minimum lumen diameter(MLD)]and calcification fracture number,minimum stent area(MSA),stent expansion coefficient(expansion,EXP),etc.Results There were 26 patients(2 with opening lesions,7 with body lesions,and 17 with bifurcation lesions at the end of the main trunk),including 7 with stable angina pectoris(SAP),10 with unstable angina(UA),4 with acute ST-segment elevation myocardial infarction(STEMI),and 5 with non ST-segment elevation myocardial infarction(NSTEMI).The PB at the most severe site of calcification decreased by 79.50(76.00,83.75)％compared to 80.00(76.00,83.75)％after IVL(P=0.001),MLA increased by 3.39(3.14,3.68)mm2 compared to 3.38(3.14,3.67)mm2 after IVL(P=0.039),MLD increased by 3.21(3.07,3.30)mm compared to 3.20(3.07,3.30)mm after IVL(P=0.024),and there was 100％calcification rupture(1/2 cases,2/9 cases,≥3/15 cases).The stent/drug ball was successfully implanted 100％,with EXP of(89.15±4.42)％and an MSA of 7.20(6.46,7.45)mm2.No adverse events such as death,angina or recurrent myocardial infarction occurred during the 3 months follow-up after surgery.Conclusions After evaluation by IVUS and pre-treatment with IVL,PCI was successfully completed for severe calcification lesions in LM,and IVL can be used as an option for the treatment of severe calcification in LM.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

OBJECTIVE: To explore the regulatory effect of chidamide on CD8⁺ T cells in T-cell acute lymphoblastic leukemia. METHODS: The expression levels of CXCL9 and CXCL3 mRNA in Jurkat cells, lymphocytes treated with chidamide and lymphocytes co-cultured with chidamide-treated Jurkat cells were detected by fluorescence quantitative PCR. The proportion of CD8⁺ T cells in lymphocytes treated with chidamide and lymphocytes co-cultured with chidamide-treated Jurkat cells was determined by flow cytometry. RESULTS: Chidamide upregulated CXCL9 mRNA expression in Jurkat cell line in a dose-dependent manner (r=0.950). The mRNA expression of CXCL9 in chidamide 5 μmol/L group was 164 times higher than that in control group. Chidamide upregulated CXCL9 mRNA expression in lymphocytes, but the up-regulated level was significantly lower than that in Jurkat cell line treated with the same concentration of chidamide. Co-culture with chidamide treated Jurkat cells upregulated the proportion of CD8⁺ T cells in lymphocytes. CONCLUSION In T-cell acute lymphoblastic leukemia, chidamide may increase the concentration of CXCL9 in the tumor microenvironment by up-regulating the expression of CXCL9 in tumor cells, leading to an increase in the number of CD8⁺ T cells.
Humans ; CD8-Positive T-Lymphocytes ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Aminopyridines/pharmacology* ; Jurkat Cells ; RNA, Messenger ; Cell Line, Tumor ; Apoptosis ; Tumor Microenvironment

Objective: To evaluate the clinical characteristics, treatment, and prognosis of patients with paraneoplastic neurological syndrome (PNS) associated with lymphoma. Methods: Between January 2012 and May 2021, the clinical data of 11 patients with lymphoma complicated with PNS treated at Peking Union Medical College Hospital were retrospectively reviewed. Results: Among the 11 patients (8 male and 3 female) , the median onset age was 61 (range, 33-78) years. The symptoms of PNS preceded lymphoma in 10 patients. The median time from the onset of PNS to the diagnosis of lymphoma was 4 months. Of the 11 patients, one had Hodgkin's lymphoma, 8 had B-cell non-Hodgkin's lymphoma, and 2 had peripheral T-cell lymphoma. Seven patients were evaluated for onconeural antibody, of whom 2 were positive (1 for anti-Ma2 antibody and 1 for anti-Yo antibody) . Of the 11 patients, the PNS symptoms of 3 patients were located in the central nervous system, 4 were located in the peripheral nervous system, and 3 were located in the muscle. Eight of the 11 patients were treated with glucocorticoid-based immunosuppressive therapy before the diagnosis of lymphoma. Patients with central nervous system involvement and dermatomyositis responded well to glucocorticoid, whereas patients with peripheral neuropathy did not significantly benefit. All 11 patients were treated with chemotherapy after the diagnosis of lymphoma. The efficacy of chemotherapy was assessed in 9 patients, 7 cases achieved complete remission, 1 case was evaluated as stable disease, and 1 case was evaluated as disease progression. The PNS symptoms of the patients who achieved complete response were almost completely recovered. The median follow-up time was 42 (range, 4-95) months. At the end of the follow-up period, 6 of the 11 patients survived, 3 were lost to follow-up, and 2 died. The median overall survival of the whole group was not reached. Conclusions: PNS can involve various parts of the nervous system and can be associated with different types of lymphoma. Through early diagnosis and treatment, the PNS symptoms could improve in most patients who achieve complete remission of lymphoma.
Adult ; Aged ; Antibodies, Neoplasm ; Autoantibodies ; Female ; Glucocorticoids ; Humans ; Lymphoma/diagnosis* ; Male ; Middle Aged ; Paraneoplastic Syndromes, Nervous System/complications* ; Retrospective Studies

ObjectiveTo evaluate the clinical efficacy of TDP （specific electromagnetic wave） combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type. MethodA total of 104 patients with knee osteoarthritis of Qi stagnation and blood stasis type， who received conservative therapy in The Third People's Hospital of Xinjiang Uygur Autonomous Region from July 2019 to December 2021， were randomized into the control group and study group with the random number table method， 52 cases in either group. The control group was treated with TDP， and the study group with TDP and Osteoking. The treatment lasted 1 week for both groups， with 1-month follow-up. Subjective indexes of visual analog scale （VAS） score and Western Ontario McMaster Universities Osteoarthritis Index （WOMAC） score， and objective indexes of visual tenderness index and visual knee range of motion were determined before and after treatment to evaluate the pain and functions of patients. Traditional Chinese medicine （TCM） syndrome score was calculated. The serum erythrocyte sedimentation rate （ESR） and high sensitivity C-reactive protein （hs-CRP） were detected before and after treatment， and the total clinical effective rate was calculated. ResultBefore treatment， the baseline information and all the scores of the two groups were comparable. After treatment， the VAS score， WOMAC score， tenderness index， knee range of motion， and TCM syndrome score were improved in both groups （P<0.01）. After the treatment， the VAS score and WOMAC score of the study group were lower than those of the control group （P<0.01） and the improvement of tenderness index in the study group was better than that in the control group （P<0.05）. The knee range of motion in the study group was better than that in the control group （P=0.061）. The TCM syndrome score of study group was lower than that of control group （P<0.01） after treatment. The post-treatment serum ESR and hs-CRP level in the two groups decreased significantly after treatment， and the study group were lower than those of the control group （P<0.01）. The total clinical effective rate of the study group was 90.4%（47/52）， as compared with the 53.8%（28/52） in the control group （P<0.05）. No obvious adverse events occurred during treatment in both groups. ConclusionThe clinical efficacy of TDP combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type is remarkable， which can improve knee pain and functions， alleviate TCM syndrome， and reduce inflammatory indexes， with high safety.

OBJECTIVE: To explore the role of chidamide in the regulatory mechanism of PD-1/PD-L1 immune escape signaling pathway in peripheral T-cell lymphoma. METHODS: Jurkat cell line was treated with different concentrations of chidamide. The changes of PD-L1 and JAK/STAT pathway gene mRNA expression and PD-L1 protein expression on cell surface were detected by fluorescence quantitative PCR and flow cytometry after treatment. RESULTS: Chidamide upregulated PD-L1 mRNA expression in Jurkat cell line in a dose-dependent manner (r=0.989). The mRNA expression of PD-L1 in 5.0 μmol/L group was 15.4 times higher than that in the control group. The proportion of PD-L1 positive cells in Jurkat cell line was less than 0.5%. Chidamide upregulated PD-L1 protein expression on Jurkat cell surface. Chidamide upregulated the mRNA expression of JAK2, STAT1 and STAT3 in Jurkat cell line. The level of up-regulation was obvious in high concentration group (5.0 μmol/L group). Meanwhile, the mRNA expression of SOCS1 and SOCS3, the negative regulatory genes upstream of the JAK/STA T pathway, were up-regulated. CONCLUSION In peripheral T-cell lymphoma, chidamide may up-regulate the expression of cell surface PD-L1 and induce T-cell chemokines by upregulation of STAT1 expression, thus improving the reaction rate of PD-1 monoclonal antibody and T-cell toxicity.
Humans ; Lymphoma, T-Cell, Peripheral ; Histone Deacetylase Inhibitors ; B7-H1 Antigen ; Janus Kinases ; Programmed Cell Death 1 Receptor ; Signal Transduction ; STAT Transcription Factors

This study aims to acetylate Rehmannia glutinosa polysaccharides by acetic anhydride method, optimize process parameters and evaluate their antioxidant activity. With the degree of substitution(D_s) as a criterion, the effects of reaction time, acetic anhydride-to-polysaccharides ratio and temperature were investigated. Process parameters were optimized by single-factor experiment and response surface methodology. The infrared spectroscopy(IR) and scanning electron microscopy(SEM) proved the successful acetylation and were employed to preliminarily analyze the structural characteristics of acetylated derivatives. The results showed that the D_s was 0.327 under the optimal technological conditions, including m(acetic anhydride):m(R. glutinosa polysaccharides)=2.70, reaction time 3.0 h and temperature 48 ℃. Further, the antioxidant properties of acetylated derivatives were investigated in vitro and acetylation was found effective to improve the antioxidant activity of R. glutinosa polysaccharides. This study provides a reference for the further development and application of R. glutinosa polysaccharides.
Acetylation ; Antioxidants/pharmacology* ; Polysaccharides/pharmacology* ; Rehmannia/chemistry*

Objective: We investigated the impact of MYC/BCL-2 protein co-expression on the prognosis of diffuse large B-cell lymphoma (DLBCL) patients and observed whether double expression (DE) remains an independent poor prognostic factor in DLBCL after the addition of therapeutic factors such as DA-EPOCH-R, central prophylaxis, and transplantation. Methods: Available pathological findings were retrospectively collected from 223 DLBCL patients at the Peking Union Medical College Hospital from 2015 to 2018. Seventy-five patients with high MYC/BCL-2 expression were categorized as the DE group. From the 148 non-DE patients, 75 DLBCL patients were selected as the control group, using a 1∶1 matching on propensity scores for age, international prognostic index score, treatment choice, and etc. The differences in overall survival (OS) and progression-free survival (PFS) between the two groups were compared. Results: The 3-year OS was (69.8±5.5) % for the DE group and (77.0±4.9) % for the non-DE group (P=0.225) , while the 3-year PFS was (60.7±5.8) % and (65.3±5.5) % , respectively (P=0.390) . Subgroup analysis in patients treated with the R-CHOP regimen revealed that for the DE and non-DE patients, the 3-year OS was (61.3±7.5) % and (77.2±5.6) % (P=0.027) , and the 3-year PFS was (52.1±7.5) % and (70.6±6.0) % (P=0.040) , respectively. Multivariate analysis showed that age, stage of Ann Arbor, COO staging, whether central prophylaxis was performed, and whether transplantation was performed were significant independent risk factors of the prognosis of DLBCL patients (P<0.05) . On the other hand, MYC/BCL-2 protein double expression was not significantly associated with prognostic outcomes. Conclusion: MYC/BCL-2 protein double expression was significantly associated with poor prognosis under R-CHOP regimen treatment, but the poor prognostic impact of DE on DLBCL was eliminated under intensive regimens such as DA-EPOCH-R and transplantation.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Doxorubicin/therapeutic use* ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prognosis ; Propensity Score ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-myc ; Retrospective Studies ; Rituximab/therapeutic use* ; Vincristine/therapeutic use*