Posterior segment involvement in systemic lupus erythematosus – A series from South India

Purpose: To report the spectrum of posterior segment manifestations and visual outcomes in a large series of patients with systemic lupus erythematosus (SLE). Methods: Retrospective study at a tertiary referral eye center in south India between 2016 and 2022. Results: Charts of 109 patients diagnosed to have SLE were retrieved from our medical database. Only nine cases of SLE (8.25%) had posterior segment involvement. The male: female ratio was 1:8. The mean age was 28 years. Unilaterality was the most common presentation in eight cases (88.89%). Lupus nephritis was the most common systemic presentation in five cases (55.56%). Antiphospholipid antibodies (APLA) positivity was seen in two cases (22.22%). Ocular manifestations included microangiopathy (cotton wool spots) in one case, occlusive retinal vasculitis with cotton wool spots in four cases (five eyes), optic disc edema with combined venous and arterial occlusion (one case), central retinal vein occlusion with cotton wool spots and hemorrhages (one case), macular edema (four cases), posterior scleritis with optic disc edema and exudative retinal detachment in the posterior pole (one case), and tubercular choroidal granuloma (one case). Treatment included systemic steroids, hydroxychloroquine sulfate (HCQS), and immunosuppression in all cases, blood thinners in two cases, and laser photocoagulation in four cases. HCQS?related retinal toxicity was not seen in any of the 109 cases. Ocular manifestation was the initial presentation of SLE in one case. Visual outcome was poor in three cases. Conclusion: Presence of posterior segment findings in cases with SLE may suggest a severe systemic disease. Early detection and aggressive treatment result in better visual outcomes. Ophthalmologists could play a vital role in guiding systemic therapy.

Risk factors of systemic lupus erythematosus: an overview of systematic reviews and Mendelian randomization studies

Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

The effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B cells and CD4+T cells in peripheral blood of patients with systemic lupus erythematosus

Abstract Background The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail. Methods PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/−cells and PD-L1+/−cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA. Results The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1− cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1− cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs. Conclusions Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1− and PD-1− cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis

Abstract Objectives BDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE. Methods We searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle-Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4. Results The final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [− 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [− 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R2 were 26.89%, 16.53%, 18.8%, and 49.96%, respectively). Conclusion In conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

Impact of baseline fluorescent antinuclear antibody positivity on the clinical outcome of patients with primary autoimmune hemolytic anemia

Abstract Introduction Autoimmune haemolytic anaemia (AIHA) is an autoimmune disorder that can present in primary or secondary forms. The literature looking at impact of baseline fluorescent antinuclear antibody (FANA) positivity on outcomes of AIHA patients is infrequent. Objective To study the impact of baseline FANA positivity in patients with primary AIHA. Method A prospective cohort study involving 29 consecutive primary AIHA patients presenting to the Haematology department from 2013 to 2015 was analysed. After recording baseline investigations including fluorescent ANA, all patients were treated as per the standard therapeutic protocols. Clinical remission, disease free survival, relapse, mortality were compared between the FANA positive and FANA Negative AIHA groups. Results Baseline FANA positivity was found in 17 patients (58.62%). Both the groups were comparable in terms of age, sex, Hemoglobin, LDH at presentation, number of lines of treatment needed and duration of follow up. Evan's syndrome was seen in six of FANA positive patients which was statistically significant (0 v/s 6, p= 0.023). FANA positive patients had significantly higher rates of relapse per patient month follow up (1.22 v/s 3.57, p= 0.023) and lower rates of complete response (83.33% v/s 35.29%, p= 0.0118) and relapse free survival at five years. Morbidity and mortality were numerically higher in FANA positive patients. Conclusion Baseline FANA positivity among AIHA patients was found to be associated with lower complete response rates and higher relapse rates with possible higher rates of morbidity. Presence of FANA will give us prognostic value and help us in deciding the treatment options.

Association between sleep and obesity in adults / 预防医学

Objective@#To examine the associations of sleep with overweight/obesity and central obesity in adults, so as to provide insights into improving sleep quality and preventing obesity in adults.@*Methods@#Demographics, height, body weight, waist circumstance and sleep status were collected from the Hubei Provincial Surveillance Program for Adult Chronic Diseases and Their Risk Factors in 2020. Subjects' sleep condiction, overweight/obesity and central obesity were descriptively analyzed. The associations of sleep with overweight/obesity and central obesity were examined using a multivariable logistic regression model.@*Results@#A total of 17 789 participants were recruited, with an average age of (56.21±13.05) years, 61.50% women, and mean duration of (7.18±1.56) h/d. There were 7 019 participants with snoring/asphyxia/suffocation (39.46%), 6 108 participants with sleep difficulty (34.34%), 8 064 participants with night waking at least twice (45.33%), 268 participants taking hypnotics (1.51%), and 6 267 participants with early morning awakening and difficulty in sleep again (35.23%), and there were 8 960 participants with overweight/obesity (50.37%) and 6 148 participants with central obesity (34.56%). Multivariable logistic regression analysis showed that sleep duration of <7 h/d (OR=1.081, 95%CI: 1.007-1.159), snoring/asphyxia/suffocation (OR=2.367, 95%CI: 2.222-2.521), and night waking at least twice (OR=1.106, 95%CI: 1.028-1.191) significantly correlated with overweight/obesity, and sleep duration of >8 h/d (OR=0.834, 95%CI: 0.761-0.913), snoring/asphyxia/suffocation (OR=2.153, 95%CI: 2.019-2.297), and night waking at least twice (OR=1.193, 95%CI: 1.105-1.288) were statistically associated with central obesity.@*Conclusion@#Sleep duration, snoring/asphyxia/suffocation and night waking are associated with overweight/obesity and central obesity.

Secondary herpes zoster wound cured by allogeneic platelet-rich plasma: a case report / 中国输血杂志

【Objective】 To investigate the feasibility of allogeneic platelet-rich plasma (PRP) for the treatment of herpes zoster wounds secondary to systemic lupus erythematosus (SLE), especially large ulcer wounds. 【Methods】 The treatment process of a patient with massive herpes zoster wounds in perineum and hip accompanied by extensive soft tissue necrosis secondary to SLE was retrospectively analyzed. The clinical efficacy of allogeneic PRP was explored combined with treatment key points and literature review. 【Results】 The patient′s wound bed was prepared until the wound was fresh, then treated externally with allogeneic PRP 3 times a week. The wound was healed completely after 42 days. 【Conclusion】 In the case of autologous PRP unavailable or unsuitable, allogeneic PRP is a safe alternative, which can effectively promote tissue regeneration, and this patient achieved curative effect in a short period of time.

Research progress of tradition Chinese medicine treatment mechanism of systemic lupus erythematosus based on biomarkers / 药学实践杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. There are still many limitations and individual differences in the treatment based on glucocorticoids and immunosuppressants. In recent years, more and more studies have shown that the combination of traditional Chinese medicine in the treatment of SLE has the advantages of good efficacy, low adverse reactions, and high safety. However, the exact regulatory mechanism and combined traditional Chinese medicine in the treatment of SLE are still unclear. This paper reviews the research on the mechanism of traditional Chinese medicine in the treatment of SLE from metabonomic, immune cells, lymphocyte factors and apoptosis, etc, provides ideas for exploring the mechanism of traditional Chinese medicine in the treatment of SLE with modern methods.

A Teenage Boy with Systemic Lupus Erythematosus Complicated with Acquired von Willebrand Syndrome: A Rare Case and Challenging in Making Diagnosis

@#In systemic lupus erythematosus (SLE), haematological abnormalities are frequent, although they are an uncommon cause of acquired von Willebrand syndrome (AVWS). AVWS is a rare condition that can cause a bleeding disorder. We presented a case of AVWS in the early diagnosis of SLE. One month before admission, the patient had a history of recurrent epistaxis. He presented to the hospital with symptomatic anaemia and was noted to have severe anaemia with iron deficiency. During hospitalisation, recurrent epistaxis recurred and was found to have prolonged activated partial thromboplastin time (aPTT), presence of lupus anticoagulant (LA), and lower von Willebrand factor (VWF), and factor 8 (VIII) levels. Simultaneously, he was diagnosed with SLE based on Systemic Lupus International Collaborating Clinics (SLICC) criteria. He underwent blood transfusions and was treated with immunosuppressive drugs such as steroids, mycophenolate mofetil, and an anti-fibrinolytic agent; he subsequently stopped bleeding and showed clinical improvement.

COVID-19 and mortality in patients with systemic lupus erythematosus

In december 2019, a new disease erupted in Wuhan, China, caused by coronavirus 2019 (CO-VID-19), which produces severe acute respiratory syndrome (SARS-CoV-2). Some cases associate COVID-19 with autoimmune disorders; the role of this virus in autoimmunity is poorly understood. Systemic lupus erythematosus (SLE) is an autoimmune disorder. Baricitinib is a Janus kinase inhibitor (JAK) approved for the treatment of autoimmune and inflam matory disorders, recently used for treating severe COVID-19 disease. We discuss four cases of SLE with COVID-19, two of whom were admitted to the intensive care unit and died, with a history of lupus nephritis; the following two cases survived. The risk fac tors which increase mortality in SLE are not yet known; however, lupus nephritis was associated with COVID-19 mortality. More studies are needed to understand the risk between autoimmune disorders and COVID-19. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2551).

Desde diciembre de 2019 estalló en Wuhan, China, una nueva enfermedad causada por corona-virus 2019 (COVID-19), causante del síndrome respiratorio agudo severo (SARS-CoV-2). Algunos casos asocian al COVID-19 a trastornos autoinmunes, el papel de este virus en la autoinmunidad está poco dilucidada. El lupus eritematoso sistémico (LES) es una enfermedad autoinmune. El baricitinib es una molécula inhibidora de quinasa de Janus (JAK) aprobada para el tratamiento de trastornos autoinmunitarios e inflamatorios, recientemente utilizado para el manejo de la enfermedad grave por COVID-19. Se trata de cuatro casos de LES con COVID-19, dos de las cuales ingresaron a la unidad de cuidados intensivos y fallecieron con antecedente de nefritis lúpica, los dos casos siguientes so brevivieron. Aún se desconocen los factores de riesgo que incrementan la mortalidad en LES; sin embargo, se asoció nefritis lúpica con mortalidad en COVID-19. Se requieren más estudios para comprender el riesgo entre las enfermedades autoinmunes y COVID-19. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2551).

Systemic lupus erythematosus patient on steroid therapy that develop to a Stevens-Johnson syndrome: a case report

Stevens-Johnson syndrome (SJS) is a cutaneous immunity reaction involving the skin and mucosa and is an emergency condition that can be fatal. The incidence of this disease is relatively rare in the range of 1-2 per 1.000.000 population. The pathogenesis of SJS involves the immune system response ofantigenic drug to body tissuesbut it still cannot be fully explained to date.We reported a woman, 35 years old with systemic lupus erythematosus (SLE) who had been on steroid therapy and in the course of treatment developed into SJSafter administration of anti-epileptic drug. Steroidshaveanti-inflammatory effects mainly due to decreased syntheses or suppression of inflammatory mediators.SJSstill can develop in patient with SLE who had been on steroid therapy. Giving steroid that indicated for the treatment of a disease including SLE, cannot prevent the occurrence of an allergic event including SJS.The presence of steroid can extend the duration of starting the drug with the occurrence of SJS and reduce the severity of the disease. Steroid still have a role in treatment that can be used both in SJS and SLE.

COVID-19 pneumonitis and lupus pneumonitis: a challenge in diagnosis and early therapeutic consideration

Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It has various clinical manifestations, from asymptomatic to severe disease with possible multi-organ involvement, with respiratory and vascular systems being the frequent affected. COVID-19 can affect patients with autoimmune diseases including systemic lupus erythematosus (SLE). The concurrent of both diseases may show the similar characteristic which can asa challenge in diagnosis and early therapeutic consideration. We report a case of 53 year-old Balinese woman patient who previously diagnosed with acute respiratory iIlness (Pneumonitis),The patient with past history of SLE since 2005, takes 200 mg hydroxychloroquine (HCQ) and 4 mg methylprednisolone once a day orally without adverse effect. Then she was confirmed with SARS-CoV-2 infection (COVID-19 pneumonitis) concurrent with SLE flare (Lupus pneumonitis). The clinical similarities were fever, dry coughand shortness of breath with the chest X-ray(CXR) was bilateral interstitiil infiltrate. Laboratory results; a positive SARS-CoV-2 polymerase chain reaction test, leucophenia, increased ESR, slightly increased CRP, decreased CD4 and CD8 cell count. Decreasedoxygen saturation, requiring 4 L of oxygen via nasal cannula on admission.She was given therapyofantibiotics, antivirus and other symptomatic. The prior SLE maintenance therapywas continued with increasingmethylprednisolone dose. The patient抯condition was improved and weaned off her oxygen requirements. Shewas dischargedandfollowed by home isolation for 14 days.

Cardiac Tamponade an Unusual Presentation of SLE — A Case Report

Systemic Lupus Erythematous (SLE) is an immune mediated disease, having variety of clinical manifestations but Cardiac Tamponade is rare as initial presentation. We are presenting an unusual case of cardiac tamponade as initial manifestation of SLE, which was also associated with Mitral Valve Vegetation, Posterior Reversible Encephalopathy Syndrome (PRESS); successfully responded to Pericardiocentesis, Steroids and Antimalarials

Association between sleep duration and hypertension among adults in Zhejiang Province / 预防医学

Objective@#To investigation the correlation between sleep duration and hypertension among adults in Zhejiang Province, and to provide scientific evidence for the prevention and control of hypertension.@*Methods@#Permanent residents at age of 18 years and older were enrolled from 10 surveillance sites for risk factors of chronic diseases included in the 2018 China Chronic Diseases and Risk Factors Surveillance Program. Subjects' demographic characteristics, smoking, alcohol consumption, sleep duration and development of hypertension were collected, and following complex weighting calculations, the association between sleep duration and hypertension were examined using a multivariable logistic regression model.@*Results@#Totally 5 770 adults were included, including 2 952 men (50.72%) and 3 178 women (49.28%), and the prevalence of hypertension was 29.39% (2 702 cases). There were 712 (8.37%), 1 077 (18.77%), 1 582 (28.68%), 1 717 (34.60%) and 682 adults (9.57%) with sleep duration of <6 h/d, 6 to 7 h/d, 7 to 8 h/d, 8 to 9 h/d and 9 h/d and longer, respectively. Taking the sleep duration of 7 to 8 h/d as a reference, multivariable logistic regression analysis identified a significant association between sleep duration of <6 h/d and the risk of hypertension (OR=1.709, 95%CI: 1.184-2.466), a significant association between sleep duration of 9 h/d and longer and the risk of hypertension (OR=1.369, 95%CI: 1.006-1.862) in men, significant associations between sleep duration of <6 h/d (OR=2.174, 95%CI: 1.528-3.093) and 6 to 7 h/d (OR=1.412, 95%CI: 1.078-1.850) and the risk of hypertension in women, and significant associations between sleep duration of <6 h/d (OR=3.095, 95%CI: 1.025-9.347) and 6 to 7 h/d (OR=2.046, 95%CI: 1.156-3.622) and the risk of hypertension in residents at ages of 18 to 44 years.@*Conclusions@#Short sleep duration may increase the risk of hypertension among adults at ages of 18 to 44 years in Zhejiang Province. Short sleep duration may increase the risk of hypertension in women and long sleep duration may increase the risk of hypertension in men.

Factors affecting poor eyesight among primary and middle schoolstudents in Tongzhou District / 预防医学

Objective@#To investigate the prevalence and influencing factors of poor eyesight among primary and middle school students in Tongzhou District, Beijing Municipality, so as to provide the evidence for developing control strategies for poor eyesight among primary and middle school students.@* Methods@#Grades 3 to 6 students in district- and township-level primary schools, grades 1 to 3 students in district- and township-level junior high schools, and grades 1 to 3 district- and township-level high schools were sampled in Tongzhou District using the stratified cluster sampling method from 2020 to 2021. Basic information, daily activity, sleep duration and eye-using habits were collected using the specific questionnaires for poor eyesight and influencing factors among students in the 2018 national program for common diseases and health risk factors surveillance program among Chinese students, and the height and body weight were measured. Factors affecting poor eyesight were among primary and middle school students identified using a multivariable logistic regression model. @*Results@#A total of 771 valid questionnaires were recovered, and the respondents included 392 male students (50.84%) and 379 female students (49.16%), and 321 primary school students (41.63%), 228 junior high school students (29.57%) and 222 high school students (28.79%). The prevalence of poor eyesight was 73.54% among the respondents. Multivariable logistic regression analysis showed that education phase (junior high school, OR=2.940, 95%CI: 1.931-4.476; high school, OR=5.998, 95%CI: 3.701-9.723) , obesity (OR=1.989, 95%CI: 1.258-3.146), daily exercise duration of less than 1 h (OR=1.931, 95%CI: 1.351-2.760), daily sleep duration of less than 8 h (OR=1.719, 95%CI: 1.193-2.477), at least 33 cm distance between a reading book and eyes (sometimes, OR=2.165, 95%CI: 1.320-3.550; never, OR=2.634, 95%CI: 1.767-3.928) and continuous short-distance eye use duration of 1 h and longer (OR=1.455, 95%CI: 1.020-2.078) were associated with poor eyesight among primary and middle school students.@*Conclusions@# The prevalence of poor eyesight is high among primary and middle school students in Tongzhou District. Higher grade, obesity, inadequate exercise and sleep duration and poor eye-using habits may increase the risk of poor eyesight.

Research progress on the effect of sleep on obesity among adults / 预防医学

Abstract@#Obesity is a major global public health problem. Long-term sleep deprivation has been identified as a major risk factor of obesity among adults, and oversleeping is found to correlate with the increased risk of obesity. Based on systematic reviews, meta-analysis and prospective cohort studies of the association between sleep and obesity among adults published during the period between 2017 and April, 2022, this review summarizes the direct impact of sleep on obesity among adults, the improvements of adult obesity by sleep and the immune, endocrine, energy metabolism, dietary habit and psychological mechanisms of obesity affected by sleep, so as to provide insights into the development of interventions against adult obesity.

Total Glucosides of Paeony Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of total glucosides of paeony （TGP） on the renal injury of MRL/lpr mice based on the Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway and explore the immunological mechanism of TGP in preventing and treating systemic lupus erythematosus （SLE）. MethodMRL/lpr female mice of SPF grade were randomly divided into a model group， a dexamethasone group （0.15 g·kg-1）， and high- （0.078 g·kg-1） and low-dose （0.039 g·kg-1） TGP groups， and female C57BL/6J mice were assigned to a blank group， with 7 mice in each group. Mice in each group were treated with corresponding drugs or normal saline by gavage at the same time every day. After 4 weeks， samples were collected. The kidney and spleen were weighed， and the organ index was calculated. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels in each group were detected by biochemical assay. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the kidney. The degree of renal fibrosis was evaluated by Masson staining. The serum levels of interleukin （IL）-2， interferon （IFN）-α， IL-4， and anti-nuclear antibody （ANA） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of TLR9， MyD88， and NF-κB p65 in renal tissues was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of TLR9 and NF-κB p65 in renal tissues was detected by immunofluorescence. The protein expression of TLR9， MyD88， and NF-κB p65 in renal and spleen tissues was tested by Western blot. ResultCompared with the blank group， the model group showed increased SCr， BUN， spleen index， and kidney index （P<0.05）， deteriorated pathological injury and fibrosis in renal tissues， elevated serum levels of IFN-α， IL-4， and ANA， decreased level of IL-2 （P<0.05）， and up-regulated TLR9， MyD88， and NF-κB p65 mRNA and protein levels in the kidney and spleen （P<0.05）. Compared with the model group， the TGP groups displayed reduced SCr， BUN， spleen index， and kidney index （P<0.05）， relieved pathological damage and fibrosis in renal tissues， decreased serum levels of IFN-α， IL-4， and ANA （P<0.05）， increased level of IL-2， and declining mRNA and protein expression levels of TLR9， MyD88， and NF-κB p65 in the kidney and spleen （P<0.05）. ConclusionTGP may inhibit the expression of downstream inflammatory factors to regulate immunity and resist SLE-induced renal injury by regulating the TLR9/MyD88/NF-κB signaling pathway.

The Role of the JAK/STAT Signaling Pathway in Steroid-induced Necrosis of Femoral Heads in MRL/lpr Iupus Mice / 中国生物化学与分子生物学报

Osteonecrosis of femoral head (ONFH) is one of the complications of systemic lupus erythematosus (SLE), which is characterized by complex pathogenesis and difficult treatment, and is the main cause of SLE-induced disability. Previous studies have confirmed that the JAK/STAT signaling pathway is involved in the pathological process of SLE, and the activation of JAK/STAT has also been found to be related to the occurrence of ONFH. Therefore, we speculated that the JAK/STAT signaling pathway may play an important role in the occurrence and development of SLE-ONFH. 30 female MRL/lpr mice were randomly divided into three groups: the model group (Lipopolysaccharide/24 hours, twice + Methylprednisolone/24 hours, 3 times), the control group (equal amount of PBS) and the treatment group (the model group + JAK1/2 inhibitors Baricitinib/day, 6 weeks), with 10 mice in each group. The results showed that the grip value of the model group was significantly lower than that of the control group at the 4th and 6th week (P < 0. 05), and that of the treatment group was better than that of the model group at the 6th week (P < 0. 05). At the 6th week, the mice were sacrificed to take the bilateral femoral head, and the morphology and HE staining pathological changes of the femoral head were observed. The results showed that the femoral head of the control group was spherical, transparent, hard and without cartilage defects, while that of the model group was irregular, rough, gray in color and partial defects of the femoral head. The performance of the mice in the treatment group was basically similar to that in the model group. And the overall appearance of the femoral head was more irregular than that in the control group. The color was darker than that in the control group, and there was a partial defect of the femoral head, but the degree was not as serious as that in the model group. The empty bone lacuna rate in the model group and treatment group were significantly higher than that in the control group (P < 0. 05), and the empty bone lacuna rate in the treatment group was lower than that in the model group (P < 0. 05). Western blotting, ELISA and RT-qPCR were used to detect the protein expression, phosphorylation levels, mRNA expression of the JAK/STAT pathway (JAK1, JAK2, JAK3, STAT3) in local bone tissues, and the expression of IL-6 and TNF- α in serum and local tissues. The mRNA expression of IL-6, TNF-α and STAT3 in bone tissues of the model group were significantly higher than that of the control group and treatment group, and the content of serum IL-6 and TNF- α of the model group were significantly higher than that of the treatment group and control group. The cartilage catabolic metabolites ADAMTS-4, MMP-13 and JAK/STAT pathway related proteins JAK1, p-JAK1, JAK2, p-JAK2, STAT3 and pSTAT3 in the model group were significantly higher than those in the control group and treatment group. In summary, the JAK/STAT signaling pathway is involved in the pathogenesis of ONFH in MRL/lpr lupus erythematosus mice. Selective JAK1/2 inhibitors can effectively inhibit ONFH inflammation, improve bone structures and joint functions, and may become an effective therapeutic drug for SLE ONFH.

Osteoporosis and osteonecrosis in systemic lupus erythematosus / Osteoporosis y osteonecrosis en el lupus eritematoso sistémico

ABSTRACT Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines.

RESUMEN La mitad de los pacientes con lupus eritematoso sistémico (LES) tendrá una densidad ósea disminuida, y más de uno de cada 10 desarrollará osteoporosis (OP) prematuramente. Son múltiples los factores de riesgo que se han relacionado con la pérdida de la masa ósea, pero solo unos pocos son modificables, tales como la ingesta de niveles adecuados de vitamina D y de calcio, ejercicio con pesas, controlar la actividad del LES, y limitar el uso de glucocorticoides (GC). También se ha encontrado una estrecha relación entre el uso de GC y osteonecrosis o a necrosis avascular (NAV). Las principales consecuencias de la OP y de la NAV son fracturas, que generan una limitación funcional importante, pérdida de la calidad de vida y aumento de la morbilidad. Las fracturas por osteoporosis se pueden reducir mediante un tamizaje adecuado con densitometría ósea y administrando tratamiento profiláctico cuando se requieren GC de largo plazo o a altas dosis. No existe un tamizaje formal para la NAV, pero su diagnóstico se realiza con imágenes (radiografía, gammagrafía ósea o imágenes avanzadas cuando corresponda). El apuntar a la menor dosis posible de GC, en combinación con inmunosupresión, además de la temprana identificación de los síntomas, ayudará a prevenir otras complicaciones. El presente artículo es una revisión práctica de la epidemiología, la fisiopatología y el manejo de la OP y la NAV en pacientes con LES, en función de la evidencia y de las guías disponibles.

Intestinal microbiota and active systemic lupus erythematosus: a systematic review

Abstract Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by being multi-systemic and, therefore, reaching various organs and affecting mainly young women. Its pathogenesis comprehends many factors, including the interaction between microbiota and immune system. This systematic review assessed the relationship between intestinal microbiota and SLE in activity, highlighting microbiota representative patterns regarding quantity and diversity. Methods: This study considered researches carried out in patients with SLE, with no restriction of age or gender, which fulfilled the classification criteria of either Systemic Lupus International Collaborating Clinic (SLICC), American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) and used the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to classify disease in activity or remission were included. The search was carried out from October, 2020 to January, 2021 using the following databases: Medline via Pubmed, Scopus, and Embase. Five papers were included with a total of 288 participants with SLE. Results: Regarding microbiota in patients with SLE in activity, there was significant increase in the following genera: Lactobacillus, Streptococcus, Megasphaera, Fusobacterium, Veillonella, Oribacterium, Odoribacter, Blautia, and Campylobacter. On the other hand, decrease in Faecalibacterium and Roseburia genera as well as Ruminococcus gnavus species was observed in remission cases, showing differences between the microbiota profile in SLE in activity and in remission. Conclusions: Results suggest that dysbiosis may be involved in the disease activity process. Trial registration: CRD42021229322 .