Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Purpose To explore the cardioprotective effect of cang-ai volatile oil(CAVO)on rats with cardiac function impairment model under low-pressure and low-oxygen environment in Tibet Plateau based on 7.0T cardiovascular magnetic resonance(CMR)imaging.Materials and Methods Forty SD rats were randomly divided into the normal group,the high altitude model group,the CAVO-treated group and the rhodiola rosea-treated group,with 10 rats in each group.Except for the normal group,the rats in other groups were transferred from the plain(500 m above sea level)to the Tibet Plateau(4 250 m above sea level)for two months,and then administered with the corresponding drugs by gavage for 14 d.The left ventricle function was measured by using a 7.0T high-field strength CMR and myocardial strain was analysed by using tissue tracing technique.HE staining was used to observe the morphology of cardiomyocytes,Masson staining to observe interstitial fibrosis,wheat germ agglutinin staining to observe cardiomyocyte hypertrophy,and transmission electron microscopy to observe the morphological changes of mitochondria in each group.Serum levels of creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase,cardiac troponin T,superoxide dismutase,malondialdehyde and glutathione peroxidase were detected.Intracellular reactive oxygen species levels were detected using flow cytometry.Results The left ventricular ejection fraction of rats in the CAVO-treated group was higher than that of the high altitude model group[(66.61±1.38)％vs.(60.94±3.21)％;t=3.969,P=0.032];meanwhile,the global circumferential strain of the left ventricle in the CAVO-treated group was higher than that of the high altitude model group(-25.68±1.30 vs.-22.84±1.17;t=3.967,P=0.003).HE,Masson and wheat germ agglutinin staining showed hypertrophy and necrosis as well as interstitial fibrosis and ultrastructural disruption of cardiomyocytes in the high altitude model group,which improved after CAVO treatment.The level of cardiac troponin T in the serum of rats with CAVO treatment group was significantly decreased compared with that of the high altitude model group[(314.03±20.05)pg/ml vs.(518.30±18.13)pg/ml;1=13.090,P=0.001].Conclusion CAVO treatment can reduce cardiac injury caused by low-pressure hypoxia in high altitude,and its effect can be detected dynamically and non-invasively by 7.0T high-field strength CMR.

Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]％vs.[24.6±16.7]％,thrombus core:[35.7±19.6]％vs.[11.1±10.4]％,all P＜0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]％vs.[41.7±27.0]％,thrombus core:[12.1±8.5]％vs.[35.7±19.6]％,all P＜0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]％,[8.0±7.7]％,and[8.9±5.3]％;thrombus core:[12.1±8.5]％,[9.5±4.2]％,and[15.7±11.0]％),and the differences were not statistically significant(all P＞0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]％vs.[15.7±11.0]％,P＜0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]％vs.[11.4±8.7]％,P＜0.001;thrombus core:[24.5±9.8]％vs.[7.6±6.0]％,P＜0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]％vs.[22.1±11.3]％,P＜0.001;thrombus core:[9.2±4.3]％vs.[24.5±9.8]％,P＜0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]％vs.[9.2±4.3]％,P＜0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]％vs.[8.5±5.3]％,P＞0.05;thrombus core:[17.9±8.8]％vs.[14.4±10.0]％,P＞0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]％vs.[9.4±6.3]％,P＜0.001;12weeks after surgery:[14.4±10.0]％vs.[8.5±5.3]％,P＜0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.

Objective:To compare the effects of unilateral thoracic paravertebal block with lidocaine on hemodynamic and the level of consciousness during double lumen endotracheal intubation.Methods:From June to october 2021,a total of 40 patients American Society of Anesthesiologists(ASA)physical status Ⅰ-Ⅱ,aged 19-65 years,scheduled for elective thoracic sugeries in Peking University Interna-tional Hospital block with under general anesthesia requiring orotracheal intubation were recruited and di-vided into two groups:The double-lumen endobronchial intubation(group C)and double-lumen endo-bronchial intubation after thoracic paravertebal block with lidocaine(group P).After an intravenous an-esthetic induction,the orotracheal double-lumen intubation was performed using a Macintosh direct laryn-goscopy,respectively.Invasive blood pressure(BP)and heart rate(HR)were recorded before and after anesthetic induction,immediately after intubation and 5 min after intubation with 1-minute interval and the intubation time was also noted.Rate-pressure product(RPP)were calculated.Results:After anes-thetic induction,BP and RPP in the two groups decreased significantly compared with their preinduction values.As comparison with their postinduction values,the orotracheal intubation in the two groups caused significant increases in BP,HR and RPP.Diastolic blood pressure(DBP)and mean arterial pressure(MAP)increased significantly and lasted for 1-minute in group C compared with the baseline values.Systolic blood pressure(SBP)was not significant change and DBP increased significantly immediately af-ter intubation in group P.HR of both groups after intubation were significantly higher than their baseline values and lasted for 4 min in group C,HR increased significantly immediately after intubation in group P.SBP,DBP,MAP,HR and RPP after intubation in group P were significantly lower than those of group C during the observation period.The value of BIS was similar between the two groups.Compared with group C,the incidence of SBP greater than 30％and RPP greater than 22 000 was significantly lower in group P in the observation period,and no patient in group P developed RPP greater than 22 000.At the end of the incidence of SBP less than 30％of the basal value and HR less than 30％of the baseline,no severe bradycardia occurred in both groups.Conclusion:During double-lumen endobronchial intubation,unilateral thoracic paravertebal block with lidocaine can provide less hemodynamic response and level of conscionsness.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To analyze clinical, immunoserological, and therapeutic features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to February 2024. Their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:A total of 35 patients were included, with a male-to-female ratio of 2.5∶1 (25 males and 10 females) and ages of 57.74 ± 17.12 years. Two (5.71%) patients were accompanied by psoriasis. In these patients, anti-p200 pemphigoid exhibited heterogeneous clinical phenotypes, mimicking classic bullous pemphigoid (20 cases, 57.14%), linear IgA bullous dermatosis (8 cases, 22.86%), or eczema (4 cases, 11.43%). The positive rates of direct immunofluorescence (DIF), indirect immunofluorescence on salt-split skin (ss-IIF), Western blot analysis with dermal extracts as substrates, and Western blot analysis with laminin γ1 C-terminal region (Lnγ1C) as substrates were 100% (24/24), 82.86% (29/35), 100% (35/35), and 80.64% (25/31), respectively. Among the 35 patients, treatment and follow-up information was available for analysis in 33. Six patients (18.18%) received non-glucocorticoid systemic therapy and topical glucocorticoid therapy, with a follow-up period ( M [ Q1, Q3]) of 19.50 (6.50, 69.25) months, and 1 withdrew the drugs. Sixteen patients received systemic glucocorticoids combined with traditional anti-inflammatory drugs, with a follow-up period of 13.50 (4.25, 18.00) months, the initial dose of glucocorticoids was equivalent to 0.30 - 0.50 mg·kg -1·d -1 of prednisone, and the time to disease control was 15.31 ± 5.23 days; among the 16 patients, 3 experienced fluctuations in disease condition which were alleviated by adding dapsone, and 1 discontinued glucocorticoids. Five patients (15.15%) received systemic glucocorticoids combined with immunosuppressants, with a follow-up period of 26.00 (14.00, 90.00) months, the initial dose of glucocorticoids was equivalent to 0.50 - 0.75 mg·kg -1·d -1 of prednisone, and the time to disease control was 10.20 ± 3.27 days; among the 5 patients, 2 received maintenance treatment with glucocorticoids (5 - 10 mg/d prednisone), 2 withdrew the drugs, and 1 relapsed after discontinuing glucocorticoids. One patient (3.03%) received systemic glucocorticoids combined with rituximab therapy, with a follow-up period of 53 months, and discontinued glucocorticoids thereafter. One patient (3.03%) received systemic glucocorticoids combined with dupilumab therapy, which proved to be effective. Four patients (12.12%) received systemic glucocorticoids combined with Janus kinase inhibitors, and 3 responded well. Conclusions:Anti-p200 pemphigoid presented a heterogeneous clinical profile in this series of patients, but scarring and milia were rare. Some patients showed negative results in Western blot analysis with Lnγ1C as substrates. The prognosis of anti-p200 pemphigoid was usually favorable, and most patients could achieve complete remission and ultimately discontinue medication.

Objective:To analyze clinical and immunoserological features of patients with epidermolysis bullosa acquisita (EBA) .Methods:Clinical data were collected from patients with confirmed EBA at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to January 2022, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:A total of 20 patients were collected, including 7 males and 13 females, and they were aged 41.85 ± 18.43 years. Ten patients presented with the classical phenotype of EBA, 8 with the inflammatory phenotype of EBA, and 2 with the mixed phenotype of EBA. Mucosal involvement occurred in 19 cases, nail involvement occurred in 4, scarring was observed in 9, and milia in 13. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side in 19 cases. Enzyme-linked immunosorbent assay for type Ⅶ collagen revealed positive results in 19 cases, with a diagnostic sensitivity of 95%. Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 290 000 in 16 cases, with a diagnostic sensitivity of 80%, and multiple autoantibodies against different basement membrane zone antigens were identified in 3 cases. Fifteen patients received systemic glucocorticoids, including 2 receiving combined immunosuppressive agents and 13 receiving combined anti-inflammatory agents with dapsone and colchicine as the first and second commonly used anti-inflammatory agents respectively; among 5 patients receiving non-glucocorticoid therapy, 2 with inflammatory EBA were sensitive to dapsone and colchicine, while the other 3 patients were lost to follow-up. Totally, 17 patients were followed up for an average duration of 26.21 months. Among the 17 patients, 1 achieved complete remission off therapy, 2 achieved complete remission on minimal therapy, and the remaining 14 patients achieved partial remission.Conclusions:The treatment of EBA is challenging, and anti-inflammatory agents such as dapsone and colchicine are often used. Immunoserological tests are of great value in the diagnosis of EBA.

Objective: To summarize clinical features and our experience of the diagnosis and treatment of laryngocele. Methods: Clinical data of 11 laryngocele patients in department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Shanxi Medical University from January 2012 to December 2021 were retrospectively reviewed, including 9 men and 2 women, aged from 12 to 75 years, with median age of 56 years. Electronic laryngoscope was performed in 10 of all patients, laryngeal CT in 10 and cervical color ultrasound in 5 before operation.All the operations were performed under general anesthesia, and the external cervical approach was used for external and combined laryngocele. The internal laryngocele was resected by low temperature plasma through transoral endoscopy. Patients were followed up regularly after operation to evaluate the effect. Clinical feature, types of lesions, imaging findings, surgical approaches and follow-up results were analyzed through descriptive statistical method. Results: Eleven laryngocele patients were divided into mixed type (n=6), internal type (n=4) and external type (n=1).Nine patients presented with hoarseness or dysphonia, 7 with cervical mass and 1 with airway obstruction. Surgical resections were done through external cervical approach (n=7)or transoral endoscopic approach (n=4). All the operations were successful and no complication occurred. All cases were followed up from 17 to 110 months. No recurrence was encountered. Conclusions: Laryngocele is a rare lesion with atypical clinical presentation. Preoperative imaging including CT scan and electronic laryngoscope is essential to evaluate the location, and extent of the lesion, and to make the surgical plan.Complete surgical excision is required. Surgical resection is the only effective method for the treatment of laryngocele.
Male ; Humans ; Female ; Middle Aged ; Child ; Adolescent ; Young Adult ; Adult ; Aged ; Laryngocele/pathology* ; Retrospective Studies ; Larynx/pathology* ; Laryngoscopy/methods* ; Hoarseness

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*