2022年 · 第135卷第18期

Dermatomyositis (DM) is an idiopathic inflammatory myopathy, with typical cutaneous manifestations and muscle lesions, usually involving multiple organs. Patients with antimelanoma differentiation-associated gene-5 (MDA5) DM usually present with clinical amyopathic DM (CADM), which is characterized by a series of unique skin and systemic manifestations, including skin ulcer and interstitial lung disease (ILD). Among them, ILD is the most common complication of anti-MDA5 DM, and in some cases, it can develop into rapidly progressive ILD (RP-ILD).^[1,2]

The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.

Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex.

In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P= 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower.

Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Biological agents, such as tumor necrosis factor inhibitors (TNFi), have been widely used in rheumatoid arthritis (RA) patients and greatly improved goal achievement. The aim of this study was to investigate whether conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combination was better in reducing relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity (LDA) with TNFi and MTX therapy.

RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks. Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups: (A) adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks; (B) maintaining TNFi and MTX for 60 weeks; and (C) maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks. The primary outcome was relapse.

A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized, with 24, 21, and 22 patients in groups A, B, and C, respectively. The relapse rates of groups A and B during the entire 60 weeks were comparable [10/22 (45.5%) vs. 7/20 (35.0%), χ² = 0.475, P = 0.491], however, significantly lower than that of group C [10/22 (45.5%) vs. 17/20 (85.0%), χ² = 5.517, P = 0.019; 7/20 (35.0%) vs. 17/20 (85.0%), χ² = 11.035, P = 0.004, respectively]. Taking RMB 100,000 Yuan as the threshold of willingness to pay, compared to MTX monotherapy (group C), both TNFi maintenance and triple csDMARDs therapies were cost-effective, but triple csDMARDs therapy was better.

For RA patients who have achieved LDA with TNFi and MTX, csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.

ClinicalTrials.gov, NCT02320630.

The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.

Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.

A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs. 6.7 mg/L), pain visual analogue scale (4.8 vs. 4.5), patient’s and physician’s global assessment (4.9 vs. 4.5 and 4.9 vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs. 4.0) simplified disease activity index (21.9 vs. 19.9), and clinical disease activity index (19.3 vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.

In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC.

The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues.

The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P < 0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P < 0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC (P < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway.

Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.

Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.

Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta^TM was used to obtain high-resolution images of three-dimensional organoids.

An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.

This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.

Bariatric metabolic surgery has been confirmed as an effective, safe, and feasible method for achieving weight loss, treating obesity-related diseases, and improving the quality of life. Due to its simplicity, sleeve gastrectomy (SG) has been more commonly used in the past ten years than Roux-en-Y gastric bypass (RYGB).^[1]However, RYGB is superior to SG in terms of excess weight loss effect and type 2 diabetes mellitus (T2DM) remission over a 5-year follow-up period. On the other hand, micronutritional deficiencies and gastrointestinal disorders after RYGB were established to be almost universal. Sleeve gastrectomy with jejunal bypass (SGJB) was first described by Munir Alamo in 2003.^[2]Their subsequent study revealed the effectiveness of the procedure in achieving weight loss and ameliorating T2DM remission.^[3]Similar results were recently reported by Linet al^[4]in Chinese patients. The latter authors also found that SG with jejunojejunal bypass (SG + JJB) [Figure 1A] leads to less pronounced post-operative nutritional deficiency and fewer complications than RYGB. Here, we present a new technique: sleeve gastrectomy plus uncut jejunojejunal bypass (SG uncut JJB). We tried to further simplify bypass procedures and accessed its short-term safety and efficacy.

Multiple myeloma (MM) is a hematologic malignancy in which plasma cells proliferate in the bone marrow, leading to osteolytic bone destruction. Bone involvement is present in up to 90% of patients with MM and is associated with pain and skeletal-related complications, such as pathologic vertebral compression fractures (VCFs).^[1]MM-associated VCFs cause spinal instability, back pain, spinal kyphosis, neurologic dysfunction, and subsequent respiratory complications, which markedly decrease the quality of life of affected patients.

To the Editor:Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. In recent years, the therapeutic treat-to-target (T2T) strategy was recommended for SLE.^[1]The immunosuppressive drugs are the standard of care in SLE treatment. Tacrolimus was one of the calcineurin inhibitors which was recommended in the 2019 update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association recommendations for the management of lupus nephritis (LN).^[2]However, few studies have focused on tacrolimus for the management of various extra-renal SLE manifestations [Supplementary Table 1, http://links. lww.com/CM9/B122]. There are also no T2T data about tacrolimus in SLE. So, we conducted this single-center, prospective, real-world study to better clarify the efficacy and safety of tacrolimus in various SLE manifestations and provide T2T evidence for tacrolimus.

To the Editor: Psoriasis is often associated with comorbidities such as cardiovascular diseases, obesity, and metabolic syndrome (MS). However, the prevalence of abovementioned diseases in Chinese patients with plaque psoriasis is still unknown. Recently, biologics such as tumor necrosis alpha inhibitors, interleukin-17A inhibitors have been successfully used in the treatment of plaque psoriasis. However, the effects of biological treatment on comorbidities associated with metabolism are still controversial. Study on the relationship between the comorbidities associated with metabolism and plaque psoriasis and the effects of biologics are necessary.

To the Editor:Antiphospholipid syndrome (APS) is a disorder characterized with thrombotic and obstetric events in patients with persistent positive antiphospholipid antibodies (aPL), including lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-β2 glycoprotein-I antibody (anti-β2GPI). The clinical symptoms of APS include many non-thrombotic manifestations, also called extra-criteria manifestations, including thrombocytopenia, aPL nephropathy, livedo reticularis, valve heart disease, and neurological manifestations.^[1]Previous study found primary obstetric APS patients with extra-criteria manifestations might have risk of developing thrombosis,^[2]and certain aPL types correlated with non-criteria manifestations.^[3]We conducted a retrospective study to analyze aPL-associated clinical phenotypes, especially extra-criteria manifestations. This study was approved by the Medical Ethics Committee of Peking Union Medical College Hospital. Signed informed consent was obtained from all patients.

Tothe Editor:Coronary artery aneurysms (CAAs), one of the complications of Kawasaki disease (KD), can cause myocardial ischemia, infarction, and even sudden death.^[1]Accurate thrombotic risk stratification in KD patients with CAAs is critical in determining whether patients need aggressive anticoagulation therapy.

To the Editor:Delayed diagnosis is a challenge in ankylosing spondylitis (AS), a representative phenotype of axial spondylarthritis (ax-SpA). Such delay might be improving,^[1]as there have been several updates on the diagnosis criteria of AS and ax-SpA, especially the 2009 Assessment of SpondyloArthritis International Society (ASAS),^[2]which recognized MRI as a powerful approach to detect early-stage lesions. However, there is still limited knowledge of whether the diagnostic delay has been improved in China. Therefore, we performed a comparative study of two datasets from the same hospital collected over 14 years.

To the Editor: Postpartum hemorrhage (PPH) is a serious complication of childbirth and a leading cause of maternal morbidity and mortality worldwide. Therefore, the correct and proactive treatment of PPH is key to reducing maternal mortality rates. The Bakri balloon is one treatment method for PPH. Here, we investigated the therapeutic effect, advantages, and disadvantages of the Bakri balloon to provide a theoretical basis for seeking appropriate pathological occasions and optimal timing for placing the Bakri balloon (Cook Inc., Spencer, IN, USA) and develop a more reasonable and effective method for treating PPH.

To the Editor:Gastric cancer (GC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide, with >70% cases occurring in Asian populations.^[1]The vast majority of patients with GC are diagnosed at an advanced stage, and the prognosis of patients with advanced GC is poor, and the mortality rate is high. Surgical resection is the cornerstone of treatment for GC. Chemotherapy, radiotherapy, targeted therapy, palliative surgery, and optimal supportive therapy have been used for the treatment of advanced GC. Conversion therapy may be a viable approach for extending overall survival. Since GC is a highly heterogeneous tumor, treatment should be performed according to its subtypes. Human epidermal growth factor receptor type 2 (HER2)-positive GC is a unique subtype of the disease, and its diagnosis and treatment strategy are different from those of HER2-negative GC. Patients with HER2-positive advanced GC can benefit from anti-HER2 therapy; however, there is currently no effective and standardized chemotherapy regimen for patients with HER2-negative advanced GC.

To the Editor:Cesarean section (CS) is among the most important and safe procedures in obstetrics. When medically indicated, CS can be a life-saving intervention. During the Chinese one-child policy, couples tended to choose CS for various reasons. In 2010, the CS rate in China rose to among the world’s highest.^[1]Yet, CS can also have various adverse maternal and neonatal consequences. Maternal mortality and maternal and infant complications are higher with CS compared with vaginal delivery.^[2]Over the past several decades, CS rates have increased sharply worldwide, and controlling these rates has become among the most prominent obstetric issues.

To the Editor:We read with great interest the article by Sunet al^[1]"Comparative analysis of duodenum-preserving head resection and pancreaticoduodenectomy. The most interesting result of the article is that duodenum-preserving pancreatic head resection (DPPHR) has several advantages on perioperative and long-term results. Unfortunately, after describing all the "modifications of DPPHR (Beger, Frey, and Gloor)," they did not specify which kind of modification was applied to each of the 28 patients that underwent DPPHR.