Volume 103 · Issue 43 · 2023

Since the publication of the classification criteria for axial spondyloarthritis (axSpA) by Assessment of SpondyloArthritis international Society (ASAS), a new disease concept "non-radiographic axial spondyloarthritis (nr-axSpA)" has emerged. Some domestic experts in China have translated it as "radiologically negative" axSpA, but it can easily lead to misunderstandings literally, as not all patients with nr-axSpA are completely free from radiological abnormalities. This article briefly describes the evolution of the concept of axSpA, proposes to translate the term of nr-axSpA directly rather than "radiologically negative" axSpA, compares the differences and similarities between nr-axSpA and radiologically negative axSpA, delineates the relationship between nr-axSpA and early ankylosing spondylitis, and points out not all the patients who meet the ASAS classification criteria for nr-axSpA are genuine patients with axSpA, because of the relatively low specificity of the ASAS classification criteria. Five common scenarios easily leading to misdiagnosis of nr-axSpA are exampled to remind domestic colleagues.

Sjögren′s syndrome (SjS) is one of the most prevalent rheumatic diseases. Off-label drug use is very common in the clinical practice of the treatment of SjS. In order to establish evidence-based justifications and systematically evaluate the off-label drug use in SjS treatment, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists referred to published guidelines, consensus statements, and case series, and reevaluated the outcomes of the randomized controlled trials about the marketed immunosuppressive drugs treating SjS. The single-item breakdown of the Sjögren′s tool for assessing response (STAR) which was proposed in 2022 was employed as the outcome. The committee established the corresponding clinical questions based on the population, intervention, comparison, and outcome (PICO) principle, and then carried out evidence retrieval, and synthesized meta-analysis using the grading of recommendations, assessment, development, and evaluation (GRADE) methodology. Finally, 21 recommendations addressing twelve clinical questions were formed which included two strong recommendations, fourteen weak recommendations, and five consensus-based recommendations. The overarching objective of the guideline is to provide clinicians with a rational basis for medication selection and to offer guidance to pharmacy departments for management purposes.

The development of ambulatory surgery has posed a challenge to the anesthesia management. In order to standardize the management of ambulatory surgery anesthesia, the Chinese Society of Anesthesiology established an expert group of guidelines for ambulatory surgery anesthesia. By combining the international guidelines and the development status of ambulatory surgery anesthesia at home and abroad, this evidence-based guideline for ambulatory surgery anesthesia was formulated. The guideline includes nine parts: definition of ambulatory surgery, ambulatory surgery system, selection criteria for ambulatory surgery patients, preoperative pre-rehabilitation, pre-anesthesia assessment, pre-anesthesia preparation, intraoperative anesthesia monitoring, anesthesia methods, and post-anesthesia management for ambulatory surgery. A total of 26 recommendations were formed. The guideline aims to better guide the clinical practice of ambulatory surgery anesthesia and standardize the perioperative management of ambulatory surgery.

To explore the clinical and laboratory characteristics of SF3B1 gene mutations in myeloproliferative neoplasms (MPN) patients.

The clinical data of 273 MPN patients who were diagnosed MPN and treated in the Second Hospital of Tianjin Medical University from November 2017 to March 2023 were retrospectively analyzed. There were 133 males and 140 females, with a median age M(Q₁,Q₃)of 56(46, 67) years. The molecular biology and cytogenetic characteristics were detected by second-generation sequencing (NGS) and R+G banding techniques, and the clinical and laboratory characteristics of patients with SF3B1 gene mutation were analyzed.

SF3B1 gene mutations were found in 13 patients (4.8%, 13/273).The types of SF3B1 mutations included missense (92.3%, 12/13) and nonsense mutations (7.7%, 1/13).Compared to the non-mutant cohort, patients in SF3B1 mutant cohort had older ages [68(51, 76) vs 56(45, 66)years,P=0.025], higher proportion of splenomegaly [46.2%(6/13) vs 15.8%(41/259),P=0.014]and secondary tumor [23.1%(3/13)vs 3.8%(10/260), P=0.018]with higher proportion of bone marrow blast [0.5%(0, 1.5%) vs 0(0, 0.5%),P=0.002] and lower hemoglobin[(104±36) vs (137±40) g/L,P=0.004] and hematocrit [31%(22%, 40%) vs 41%(35%, 52%),P=0.003]. All of the 10 patients in the SF3B1 mutant cohort whose ring sideroblast (RS) could be evaluated showed no RS formation. The overall survival, thrombosis-free survival and leukemia free survival of MPN patients in SF3B1 mutant cohort were 4.0 (2.0, 6.0), 2.0 (0.5, 4.5) and 4.0 (2.0, 6.0) years, respectively, while patients in the non-mutant cohort were 6.0 (3.0, 10.0), 5.0 (1.0, 8.0), 6.0 (3.0, 10.0) years, respectively, there were no statistical significance between two groups (Z=3.69, 1.66, 2.05, all P>0.05).The secondary tumor free survival of SF3B1 mutant cohort patients was 4.0 (2.0, 6.0) years, which was lower than that of non-mutant cohort patients [5.5 (3.0, 10.0) years, Z=18.18, P<0.001).

MPN patients with SF3B1 gene mutations are older, more prone to splenomegaly and secondary tumors. They also have a higher proportion of bone marrow blast, lower hemoglobin and hematocrit, and show no RS formation.

To investigate the role and related mechanism of the highly expressed circular RNA molecule 103124 (hsa_circRNA_103124) in macrophage differentiation, pyroptosis and inflammation in peripheral blood mononuclear cells (PBMC) of patients with active Crohn′s disease (CD).

Patients with active CD (CD group) admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from April to September 2018 and healthy people (control group) from the physical examination center of the hospital from July to October 2018 were retrospectively selected. The levels of hsa_circRNA_103124 and Toll-like receptor 4 (TLR4) in PBMC of the two groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Tohoku hospital pediatrics-1 (THP1) cell line was used as a model for the study of hsa_circRNA_103124 regulating macrophage differentiation. Lentivirus infection was used to construct hsa_circRNA_103124 overexpressed or down-regulated THP1 cells to induce macrophage-like differentiation. According to the expression level of hsa_circRNA_103124, THP1 cell lines were divided into the following four groups: pLC5-ciR was overexpression control group; hsa_circRNA_103124 OE was the overexpression group; ShRNActrl was down-regulated expression control group; hsa_circRNA_103124 ShRNA was the down-regulated expression group. Flow cytometry was used to detect levels cluster of differentiation (CD) 68, CD80, interleukin (IL)-6, tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS). The expression levels of IL-6, TNF-α, IL-1β, TLR4 and myeloid differentiation factor 88 (MyD88) were detected by RT-qPCR. The levels of gasdermin D (GSDMD), IL-18 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were determined by immunofluorescence and RT-qPCR. Pearson correlation analysis was used to analyze the correlation between the abundance of hsa_circRNA_103124 and TLR4 expression level or Crohn′s disease activity index (CDAI).

A total of 50 patients were included in the CD group, including 36 males and 14 females, aged (35±10) (19-64) years. A total of 30 subjects were included in the control group, including 22 males and 8 females, aged (38±9) (24-64) years. hsa_circRNA_103124 [(0.009±0.016) vs (0.003±0.002), P=0.042] and TLR4 [(0.005±0.003) vs (0.001±0.001), P<0.001] were all upregulated in the PBMC of patients in the CD group, compared with the control group. And hsa_circRNA_103124 was positively correlated with TLR4 (r=0.40, P=0.004). hsa_circRNA_103124 level was positively correlated with CDAI (r=0.32, P=0.024). The expression of CD68 (P=0.002) and CD80 (P<0.001) were enhanced. hsa_circRNA_103124 promoted production of ROS and the expression of IL-6, TNF-α, IL-1β, TLR4, MyD88, GSDMD, IL-18 and NLRP3 in macrophage-like M1 differentiated THP1 cells (all P<0.05).

High expresion of hsa_circRNA_103124 in PBMC of patients with active CD may promote macrophage M1 differentiation, pyroptosis and inflammation through enhancing the expression of TLR4, MyD88, NLRP3 and GSDMD.

To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease.

Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared.

A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05).

For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

To explore the effect of ileostomy on clinical outcomes of children with very early onset inflammatory bowel disease(VEO-IBD). The clinical data of 11 children with VEO-IBD who underwent ileostomy in the Department of Gastroenterology of the Affiliated Children′s Hospital of Zhengzhou University from January 2016 to December 2022 were retrospectively analyzed, and the clinical characteristics and outcomes were analyzed. A total of 11 cases were included, including 7 males and 4 females, aged 3.0 (0.9, 8.0) months. The main clinical manifestations were fever and diarrhea, with L2 type the main lesion site (according to the Paris classification of childhood Crohn′s disease). There were 7 cases of gene type interleukin (IL)-10RA. After VEO-IBD ileostomy, the disease site, incidence of growth disorders, the weighted children′s Crohn′s disease activity index, the simplified endoscopic score of Crohn′s disease, and severe mucosal inflammation activity rate were all lower than those before ileostomy (all P<0.05). The postoperative inflammatory indicators and factors were lower than those before ileostomy (all P<0.05). The mucosal barrier indicators after ileostomy were increased than before (all P<0.05). The nutritional evaluation indicators after ileostomy were improved (P<0.05). Ileostomy can reduce inflammatory response of VEO-IBD, improve intestinal mucosal barrier, reduce disease activity, and improve nutritional status.

Two children with chronic hepatitis B (CHB) transmitted from mother to child were admitted to the First Hospital of Lanzhou University. At the initial diagnosis, the levels of hepatitis B viral load and hepatitis B surface antigen (HBsAg) were high, accompanied by liver histological changes. They were immediately given antiviral treatment with entecavir, but HBsAg never turned negative. After subsequent treatment with peginterferon α-2b (Peg-IFN-α-2b) on the basis of entecavir, clinical cure was achieved in a short time. In the continuous follow-up of 2 children, the drug has not been stopped at present, and antiviral therapy is still used.

In recent years, new biological agents such as neonatal Fc receptor (FcRn) inhibitors have begun to be used to treat autoimmune diseases. Compared with traditional immunosuppressants, they have the advantages of fast onset of action, high selectivity, and fewer adverse reactions, which makes autoimmune patients with immune diseases have more and better choices. The combination of FcRn and IgG can prolong the half-life of IgG. FcRn inhibitors can quickly eliminate pathogenic IgG by targeting and blocking the combination of the two, achieving the effect of reducing immune damage and alleviating the disease. Multiple clinical studies have confirmed the efficacy of FcRn inhibitors on autoimmune diseases, but the long-term efficacy needs to be observed and verified by more clinical studies.

Dural arteriovenous fistula (DAVF) refers to the pathological shunt between meningeal artery and dural vein, with an incidence of 10% ~15%. Patients with atypical clinical manifestations are often misdiagnosed. Digital subtraction angiography is the preferred imaging method for the diagnosis and follow-up of DAVF. The continuous development of new non-invasive imaging diagnosis technology is helpful for the early screening and diagnosis of DAVF. Patients with low-grade DAVF are more suitable for conservative treatment, while for patients with high-grade DAVF, endovascular interventional embolization through arterial or venous approach is the first treatment method, but the appropriate approach and embolization material need to be selected according to different sites. Surgical treatment or stereotactic radiosurgery can be used as an adjunct to optimize endovascular treatment. New non-invasive auxiliary examination techniques, as well as the development of new interventional embolization materials and stereotactic radiosurgery still require further clinical studies to determine their effectiveness and safety.

Alzheimer's disease (AD) remains one of the major challenges facing human society, and its pathogenesis is still controversial. Existing human genetic evidence shows that microglia, an important immune cell in the brain, can protect other brain cells from invasion, and can remove metabolic garbage accumulated in the brain, thus delaying the degeneration of neurons. Its functional status is closely related to AD. Genome-wide association studies on sporadic late-onset AD found that myeloid cell trigger receptor 2 (Trem2) plays an important role in microglia detecting and processing neurodegeneration processes. Trem2 variation is the strongest genetic risk factor for AD. One of the factors, and activating Trem2 signaling pathway can activate the microglia response to A β and reduce A β deposition. Therefore, restoring or enhancing the defective Trem2 function in microglia may be a way to combat the damage and degeneration of AD neurons.

The prevalence of Alzheimer's disease (AD) is increasing year by year, but there is still a lack of effective treatment. Therefore, discovering and preventing controllable risk factors for AD has become one of the most important public health goals at present. Numerous evidence suggests that obesity is one of the risk factors for AD, and possible biological mechanisms for this correlation include increased levels of inflammation due to obesity, insulin resistance, and increased levels of beta-amyloid in adipose tissue. In addition, lower lean body mass (which refers to the remaining body mass except fat, a measure of muscle mass) is also associated with an increased risk of AD, but the causal or pre-post relationship between the two is not clear. The study hypothesized that "higher lean body mass can reduce the risk of AD and improve cognitive performance", and used Mendelian randomization to study the effect of lean body mass on AD risk and cognitive performance from a genetic perspective.

Most of the recent studies on relief pleasure focus on related learning behaviors, and indirectly reflect the positive emotional effects of relief pleasure through the anti-anxiety effects of behaviors, so it cannot directly confirm its own positive emotional effects. By drawing on the classical conditional position preference (CPP) behavioral model, the research team provided a quantifiable behavioral indicator for the positive emotional effect of relief pleasure-relief CPP. For the first time, this study provides a relatively complete chain of evidence for the physiological significance of relief pleasure: in correlation, the intensity of relief pleasure in individual animals is positively correlated with the toughness level of depression-like behaviors; In necessity and sufficiency, blocking or enhancing relief pleasure promotes or prevents chronic stress-induced depression-like behavior, respectively. This evidence confirms a causal relationship between relief pleasure and mental toughness, suggesting that relief pleasure may be a naturally selected natural antidepressant mechanism.

In 2009, a new subtype of acute T lymphocytic leukemia (T-ALL) was discovered, which has similar characteristics, unique gene expression profiles, and immunophenotypes to normal early T cell precursors (ETPs), and is called ETP-ALL. The immunophenotype of ETP lymphoblasts is defined as a loss of CD8 and CD1a expression, attenuated CD5 expression, and strong expression of one or more myeloid and/or stem cell markers, while "near ETP-ALL" is used to describe cases that otherwise meet the ETP-ALL immunophenotypic criteria, but express higher levels of CD5. Previous small-scale retrospective analyses have found that patients with ETP-ALL have a worse prognosis than non-ETP patients, therefore experimental therapy or hematopoietic stem cell transplantation after first remission is recommended. While minimal residual disease (MRD) levels are generally known to be high in patients with ETP, the prognosis of ETP-ALL remains unknown due to the lack of large-scale cohort studies.