Objective:To apply combined serological diagnostic methods for anti-BP180-type and anti-laminin 332 (Ln332) -type mucous membrane pemphigoid (MMP), and to summarize their clinical and immunoserological characteristics.Methods:A retrospective analysis was conducted on the data from 52 patients clinically suspected of having MMP at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to February 2022. Serum samples were collected, and combined serological tests, including indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting, were performed to analyze the immunoserological and clinical characteristics of the patients. The Fisher′s exact test was used to compare the lesion occurrence rates between groups.Results:Among the 52 patients clinically suspected of MMP, 32 (61.5%) were diagnosed with anti-BP180-type MMP, 10 (19.2%) with anti-Ln332-type MMP, and 4 (7.7%) with anti-BP180- and anti-Ln332-type MMP due to the presence of both anti-BP180 and anti-Ln332 antibodies; 2 tested positive for IgG on the epidermal side of salt-split skin, but no target antigens were identified by serological tests, and they were diagnosed with MMP (subtype pending) ; 4 tested negative by immunoserological tests. Ocular involvement was observed in 6 out of 10 patients with anti-Ln332-type MMP, whereas only 6 out of 32 anti-BP180-type MMP patients (18.8%) had ocular symptoms, and there was a significant difference in the occurrence rate of ocular involvement between the two groups ( P = 0.02) ; the occurrence rates of nasal involvement and multi-mucosal involvement were significantly higher in the anti-Ln332-type MMP patients (50%[5/10], 90%[9/10], respectively) than in the anti-BP180-type MMP patients (0, 25%[8/32], respectively, both P < 0.001). Scar formation occurred in 6 out of 10 anti-Ln332-type MMP patients, but occurred in only 6 out of 32 anti-BP180-type patients (18.8%, P = 0.02) . Conclusion:The combination of indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting could effectively identify anti-BP180 and anti-Ln332 autoantibodies in MMP patients, with BP180 being the most common target antigen; compared with anti-BP180-type MMP, anti-Ln332-type MMP appeared to be more frequently involve the ocular and nasal mucosae, associated with the involvement of multiple mucosal sites, carrying a higher risk of scar formation.

Objective To explore the incidence and its influencing factors of transient severe motion(TSM)in the arterial phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods The databases of China National Knowledge Network(CNKI),VIP,Wanfang,PubMed,and Embase were searched for studies on the incidence and influencing factors of TSM,and the search time was from the establishment of the databases to October 2024.Meta-analysis was performed via Stata 17.0 software.Results A total of 30 papers(33 studies)were finally included,totaling 12 565 patients.Meta-analysis results showed that the incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI was 13.0％.The risk factors for TSM included age[odds ratio(OR)=1.03;95％confidence interval(CI)1.02-1.05;P＜0.001),chronic obstructive pulmonary disease(COPD)(OR=4.21;95％CI 1.76-10.09;P=0.001),and moderate-to-severe pleural effusion(OR=3.34;95％CI 1.69-6.63;P=0.001),while a previous usage history of Gd-EOB-DTPA(OR=0.56;95％CI 0.39-0.81;P=0.002)was a protective factor of TSM.Conclusion The incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI is relatively high.Age,COPD,moderate-to-severe pleural effusion are risk factors for TSM,while the previous usage history of Gd-EOB-DTPA is a protective factor for TSM.

Objective:To apply combined serological diagnostic methods for anti-BP180-type and anti-laminin 332 (Ln332) -type mucous membrane pemphigoid (MMP), and to summarize their clinical and immunoserological characteristics.Methods:A retrospective analysis was conducted on the data from 52 patients clinically suspected of having MMP at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to February 2022. Serum samples were collected, and combined serological tests, including indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting, were performed to analyze the immunoserological and clinical characteristics of the patients. The Fisher′s exact test was used to compare the lesion occurrence rates between groups.Results:Among the 52 patients clinically suspected of MMP, 32 (61.5%) were diagnosed with anti-BP180-type MMP, 10 (19.2%) with anti-Ln332-type MMP, and 4 (7.7%) with anti-BP180- and anti-Ln332-type MMP due to the presence of both anti-BP180 and anti-Ln332 antibodies; 2 tested positive for IgG on the epidermal side of salt-split skin, but no target antigens were identified by serological tests, and they were diagnosed with MMP (subtype pending) ; 4 tested negative by immunoserological tests. Ocular involvement was observed in 6 out of 10 patients with anti-Ln332-type MMP, whereas only 6 out of 32 anti-BP180-type MMP patients (18.8%) had ocular symptoms, and there was a significant difference in the occurrence rate of ocular involvement between the two groups ( P = 0.02) ; the occurrence rates of nasal involvement and multi-mucosal involvement were significantly higher in the anti-Ln332-type MMP patients (50%[5/10], 90%[9/10], respectively) than in the anti-BP180-type MMP patients (0, 25%[8/32], respectively, both P < 0.001). Scar formation occurred in 6 out of 10 anti-Ln332-type MMP patients, but occurred in only 6 out of 32 anti-BP180-type patients (18.8%, P = 0.02) . Conclusion:The combination of indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting could effectively identify anti-BP180 and anti-Ln332 autoantibodies in MMP patients, with BP180 being the most common target antigen; compared with anti-BP180-type MMP, anti-Ln332-type MMP appeared to be more frequently involve the ocular and nasal mucosae, associated with the involvement of multiple mucosal sites, carrying a higher risk of scar formation.

Objective To explore the incidence and its influencing factors of transient severe motion(TSM)in the arterial phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods The databases of China National Knowledge Network(CNKI),VIP,Wanfang,PubMed,and Embase were searched for studies on the incidence and influencing factors of TSM,and the search time was from the establishment of the databases to October 2024.Meta-analysis was performed via Stata 17.0 software.Results A total of 30 papers(33 studies)were finally included,totaling 12 565 patients.Meta-analysis results showed that the incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI was 13.0％.The risk factors for TSM included age[odds ratio(OR)=1.03;95％confidence interval(CI)1.02-1.05;P＜0.001),chronic obstructive pulmonary disease(COPD)(OR=4.21;95％CI 1.76-10.09;P=0.001),and moderate-to-severe pleural effusion(OR=3.34;95％CI 1.69-6.63;P=0.001),while a previous usage history of Gd-EOB-DTPA(OR=0.56;95％CI 0.39-0.81;P=0.002)was a protective factor of TSM.Conclusion The incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI is relatively high.Age,COPD,moderate-to-severe pleural effusion are risk factors for TSM,while the previous usage history of Gd-EOB-DTPA is a protective factor for TSM.

The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of N ⁶-methyladenosine (m⁶A); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown. Herein, we designed the first FTO-targeting proteolysis targeting chimera (PROTAC) degrader QP73 using our FTO inhibitor Dac85-which potently inhibits FTO demethylation in AML cell lines-as a warhead. Notably, QP73 significantly induced FTO degradation in a time-, dose-, and ubiquitin-proteasome system-dependent manner and had superior antiproliferative activities to the FTO inhibitor Dac85 in various AML cell lines. Moreover, QP73 treatment significantly increased m⁶A modification on mRNA, promoted myeloid differentiation, and induced apoptosis of AML cells. Quantitative proteomics analysis showed that QP73 induced complete FTO degradation, upregulating RARA and ASB2 abundance and downregulating CEBPA, MYC, PFKP, and LDHB levels in AML cells. Lastly, QP73 exhibited antileukemic activity by increasing m⁶A modification and decreasing FTO levels in xenograft AML tumors. This proof-of-concept study shows that FTO-targeting PROTAC degraders can regulate the FTO signaling pathway and have potential antileukemia applications.

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 investigate the current situation of the review and comment on inpatient medical orders in Beijing municipal hospitals， and to put forward countermeasures and suggestions for further improving related work. METHODS A questionnaire survey was conducted to investigate the current situation of the review and comment on inpatient medical orders in 22 Beijing municipal hospitals. The statistical analysis was conducted for the survey results. RESULTS A total of 22 questionnaires were distributed， with recovery effective rate of 100%. The 22 hospitals carried out inpatient medical order comment， but their proportion varied among hospitals （0.88%-98.54%）； medical order comment mainly focused on antibiotics， proton pump inhibitors， anesthetic drugs/class Ⅰ psychotropic drugs， auxiliary drugs and other categories； 205 pharmacists participated in the comment of inpatient medical orders， most of whom hold intermediate or higher professional titles （89.27%）； 21 hospitals conducted inpatient medical order comment and feedback the results to relevant departments/responsible persons， but the intervention situation was not the same. Eighteen hospitals had carried out the review of inpatient medical orders； reviewed drug category was roughly the same as the category involved in the medical order comment； review content involved the suitability of administration routes， dosage， etc. The review was conducted mainly through the cooperation of audit software and pharmacists. CONCLUSIONS The comment and review of inpatient medical orders in Beijing municipal hospitals carried out in an orderly manner， and preliminary results have been achieved； at the same time， it is necessary to further increase the ability of participating pharmacists， improve audit standards， optimize pre-audit （No.ZYLX201805） software， and promote rational drug use among hospitalized patients through doctor-pharmacist collaboration.