Liangbin Zhao

Microscopic polyangiitis (MPA) is a rare autoimmune disorder characterized by small-vessel vasculitis and the presence of anti-neutrophil cytoplasmic antibody (ANCA). Typically, MPA primarily affects the respiratory system, kidneys, and skin, with infrequent involvement of the nervous system, resulting in neuropathy. However, the occurrence of subarachnoid hemorrhage (SAH) in MPA is exceedingly rare, especially when it is accompanied by hemorrhagic events in multiple organs. This case report details the clinical presentation of a 61-yearold male patient diagnosed with MPA who experienced an exceptionally uncommon occurrence of SAH, coupled with extensive bleeding manifestations including epistaxis, skin purpura, and gastrointestinal bleeding. Notably, the patient's symptoms exhibited potential improvement following a treatment regimen consisting of rituximab and glucocorticoids. This case emphasizes the critical importance of promptly recognizing and comprehensively managing rare complications in MPA patients to optimize clinical outcomes.

Background Growing evidence points a connection between Primary Sjögren's Syndrome (pSS) and Primary Biliary Cholangitis (PBC). This study seeks to identify the crosstalk genes between them. Method Transcriptomic datasets for pSS (GSE66795) and PBC (GSE119600) were sourced from the Gene Expression Omnibus (GEO) database. Common genes between these two conditions were detected using Differential Expression Analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Potential crosstalk genes were pinpointed through Least Absolute Shrinkage and Selection Operator (LASSO) regression. Validation of these genes were performed through single-sample gene set enrichment analysis (ssGSEA), multivariable logistic regression, and single-cell transcriptome analysis. Result Differential expression analysis showed 339 commonly upregulated DEGs in both pSS and PBC. WGCNA analysis revealed 11 modules associated with pSS and 7 modules associated with PBC. Subsequently, 56 core genes were found to overlap between the genes identified by differential expression analysis and WGCNA. LASSO regression identified CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L, and MUC1 as pivotal crosstalk genes for both pSS and PBC. Moreover, ssGSEA analysis and multivariable logistic regression underscored the potential of these 7 genes as crosstalk genes. Single-cell analyses revealed higher proportions of NK cells, CD4+ T cells, and CD8+ T cells in pSS patients, with prominent expression of CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L, and MUC1 in these cells. Conclusion Our study identified CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L and MUC1 as crosstalk genes between pSS and PBC, and highlighted the critical role of NK cells, CD4+ T cells and CD8+ T cells in disease mechanisms.

Background: Endometriosis (EM) is a chronic painful condition that predominantly affects women of reproductive age. Currently, surgery or medication can only provide limited symptom relief. This study used a comprehensive genetic analytical approach to explore potential drug targets for EM in the plasma proteome.Methods: In this study, 2,923 plasma proteins were selected as exposure and EM as outcome for two-sample Mendelian randomization (MR) analyses. The plasma proteomic data were derived from the UK Biobank Pharmaceutical Proteomics Project (UKB-PPP), while the EM dataset from the FinnGen consortium R10 release data. Several sensitivity analyses were performed, including summary-data-based MR (SMR) analyses, heterogeneity in dependent instruments (HEIDI) test, reverse MR analyses, steiger detection test, and bayesian co-localization analyses. Furthermore, proteome-wide association study (PWAS) and single-cell transcriptomic analyses were also conducted to validate the findings.Results: Six significant (p < 3.06 × 10^-5) plasma protein-EM pairs were identified by MR analyses. These included EPHB4 (OR = 1.40, 95% CI: 1.20 - 1.63), FSHB (OR = 3.91, 95% CI: 3.13 - 4.87), RSPO3 (OR = 1.60, 95% CI: 1.38 - 1.86), SEZ6L2 (OR = 1.44, 95% CI: 1.23 - 1.68) and WASHC3 (OR = 2.00, 95% CI: 1.54 - 2.59) were identified as risk factors, whereas KDR (OR = 0.80, 95% CI: 0.75 - 0.90) was found to be a protective factor. All six plasma proteins passed the SMR test (P < 8.33 × 10^-3), but only four plasma proteins passed the HEIDI heterogeneity test (PHEIDI > 0.05), namely FSHB, RSPO3, SEZ6L2 and EPHB4. These four proteins showed strong evidence of co-localization (PPH4 > 0.7). In particular, RSPO3 and EPHB4 were replicated in the validated PWAS. Single-cell analyses revealed high expression of SEZ6L2 and EPHB4 in stromal and epithelial cells within EM lesions, while RSPO3 exhibited elevated expression in stromal cells and fibroblasts.Conclusion: Our study identified FSHB, RSPO3, SEZ6L2, and EPHB4 as potential drug targets for EM and highlighted the critical role of stromal and epithelial cells in disease development. These findings provide new insights into the diagnosis and treatment of EM.

Background: The co-occurrence of primary biliary cholangitis (PBC) and systemic lupus erythematosus (SLE) has been consistently reported in observational studies. Nevertheless, the underlying causal correlation between these two conditions still needs to be established.Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to assess their causal association. Five MR analysis methods were utilized for causal inference, with inverse-variance weighted (IVW) selected as the primary method. The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and the IVW Radial method were applied to exclude outlying SNPs. To assess the robustness of the MR results, five sensitivity analyses were carried out. Multivariable MR (MVMR) analysis was also employed to evaluate the effect of possible confounders. In addition, we integrated transcriptomic data from PBC and SLE, employing Weighted Gene Co-expression Network Analysis (WGCNA) to explore shared genes between the two diseases. Then, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods to perform on the shared genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was utilized to identify potential shared diagnostic genes. Finally, we verified the potential shared diagnostic genes in peripheral blood mononuclear cells (PBMCs)-specific cell populations of SLE patients by single-cell analysis.Results: Our MR study provided evidence that PBC had a causal relationship with SLE (IVW, OR: 1.347, 95% CI: 1.276 - 1.422, P < 0.001) after removing outliers (MR-PRESSO, rs35464393, rs3771317; IVW Radial, rs11065987, rs12924729, rs3745516). Conversely, SLE also had a causal association with PBC (IVW, OR: 1.225, 95% CI: 1.141 - 1.315, P < 0.001) after outlier correction (MR-PRESSO, rs11065987, rs3763295, rs7774434; IVW Radial, rs2297067). Sensitivity analyses confirmed the robustness of the MR findings. MVMR analysis indicated that body mass index (BMI), smoking and drinking were not confounding factors. Moreover, bioinformatic analysis identified PARP9, ABCA1, CEACAM1, and DDX60L as promising diagnostic biomarkers for PBC and SLE. These four genes are highly expressed in CD14+ monocytes in PBMCs of SLE patients and potentially associated with innate immune responses and immune activation.Conclusion: Our study confirmed the bidirectional causal relationship between PBC and SLE and identified PARP9, ABCA1, CEACAM1, and DDX60L genes as the most potentially shared diagnostic genes between the two diseases, providing insights for the exploration of the underlying mechanisms of these disorders.

Aims Systematic low-grade inflammation is considered to be an important factor leading to the development of T2DM and the progression of its complications. Dipeptidyl-peptidase-4 (DPP-4) inhibitors show potential anti-inflammatory effects in patients with T2DM. This meta-analysis aimed to evaluate the anti-inflammatory effects of DPP-4 inhibitors in patients with T2DM. Methods A comprehensive search was performed in PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials that assess the anti-inflammatory effects of DPP-4 inhibitors. Quantitative data analysis was conducted by a random-effects model. Sensitivity analyses were conducted to determine the robustness of the pooled results. Results Twenty-two studies with 1595 patients with T2DM were included. Pooled results showed that DPP-4 inhibitor therapy was significantly associated with the reduction of C-reactive protein (CRP) (SMD, − 0.56, p < 0.01), TNF-α (SMD, − 1.69, p < 0.01), IL-6 (SMD, − 0.67, p < 0.01), and IL-1β (WMD, − 8.21 pg/ml, p < 0.01). Leave-one-out meta-analysis showed no significant change in the pooled results of CRP and TNF-α. Conclusion This meta-analysis demonstrated that DPP-4 inhibitors can significantly attenuate low-grade inflammatory state in patients with T2DM. In addition to improving glycemic control, DDP-4 inhibitors might offer extra therapeutic value by controlling inflammation. Graphical Abstract

Rationale: Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) manifestations. However, typical symptoms of catatonia are uncommon. Neuropsychiatric SLE or its “mimickers” may cause NP symptoms, making differential diagnosis a significant challenge in clinical practice. Patient concerns: A 68-year-old female with SLE was hospitalized for edema, lung infection, and recurrent fungal mouth ulcers after multiple courses of cortisol and immunosuppressive therapy. Five days after admission, stupor, immobility, mutism, and rigidity were observed. Diagnosis: “Mimickers”: catatonic disorder due to a general medical condition. Intervention: Initially, relevant laboratory tests, imaging studies, and the disease activity index score were performed. A survey of the causes of the disease was conducted among the patient’s relatives. Subsequently, we discontinued moxifloxacin, corticosteroids, fluconazole, and other medications and inserted a gastric tube for nutritional support. During this process, traditional Chinese medicine and acupuncture have been utilized. Outcomes: After 3 days, the patient recovered and only complained of fatigue. Conclusion: When SLE presents with NP symptoms, it is essential to make a correct diagnosis in order to guide appropriate treatment by actively searching for inducers and clinical, laboratory, and neuroradiological characteristics that can aid in the differential diagnosis. When treatment options are limited, it can be beneficial to try a variety of combination strategies, such as traditional Chinese medicine and acupuncture.

Rationale: Meningoencephalomyelitis and visceral dissemination infection are rare but life-threatening complications of either the primary infection or reactivation of varicella-zoster virus (VZV) in immunocompromised patients. To date, few studies have reported the co-existence of VZV meningoencephalomyelitis and the visceral dissemination of VZV infection. Patient concerns: A 23-year-old male was diagnosed with lupus nephritis class III and was being treated with oral prednisone and tacrolimus. The patient exhibited herpes zoster 21-day after the initiation of therapy and experienced unbearable abdominal pain and generalized seizures 11 days after the onset of a zoster rash. Magnetic resonance imaging showed progressive lesions in the cerebrum, brainstem, and cerebellum, as well as meningeal thickening and thoracic myelitis. Computed tomography showed pulmonary interstitial infiltration, partial intestinal dilatation, and effusion. Metagenomic next-generation sequencing revealed 198,269 and 152,222 VZV-specific reads in the cerebrospinal fluid and bronchoalveolar lavage fluid, respectively. Diagnoses: Based on the clinical and genetic findings, this patient was finally diagnosed with VZV meningoencephalomyelitis and visceral disseminated VZV infection. Interventions: The patient received intravenous acyclovir (0.5 g every 8 hours) combined with plasma exchange and intravenous immunoglobulin. Treatment against secondary bacterial and fungal infections, organ support therapy and rehabilitation training were given simultaneously. Outcome: The patient’s peripheral muscle strength did not improve and repeated metagenomic next-generation sequencing showed the persistence of VZV-specific reads in the cerebrospinal fluid. The patient finally abandoned therapy due to financial constraints at the 1-month follow-up. Lessons: Patients with autoimmune diseases receiving immunosuppressive therapy should be warned about the possibility of developing serious neurological infections and visceral disseminated VZV infections as side effects. Early diagnosis and the early initiation of intravenous acyclovir therapy are important for such cases.

Background. Persistent inflammation has been recognized as an important comorbid condition in patients with chronic kidney disease (CKD) and is associated with many complications, mortality, and progression of CKD. Previous studies have not drawn a clear conclusion about the anti‐inflammatory effects of statins in CKD. This meta‐analysis is aimed at assessing the anti‐inflammatory effects of statins therapy in patients with CKD. Methods. A comprehensive literature search was conducted in these databases (Medline, Embase, Cochrane library, and clinical trials) to identify the randomized controlled trials that assess the anti‐inflammatory effects of statins. Subgroup, sensitivity, and trim‐and‐fill analysis were conducted to determine the robustness of pooled results of the primary outcome. Results. 25 eligible studies with 7921 participants were included in this meta‐analysis. The present study showed that statins therapy was associated with a decreased C‐reactive protein (CRP) (‐2.06 mg/L; 95% CI: ‐2.85 to ‐1.27, p < 0.01). Subgroup, sensitivity, and trim‐and‐fill analysis showed that the pooled results of CPR were stable. Conclusion. This meta‐analysis demonstrates that statins supplementation has anti‐inflammatory effects in patients with CKD. Statins exert an anti‐inflammatory effect that is clinically important in improving complications, reducing mortality, and slowing progression in CKD. We believe that the benefits of statins to CKD are partly due to their anti‐inflammatory effects. However, stains usually are prescribed in the CKD patients with dyslipidemia, whether statins can reduce inflammation in CKD patients with normal serum lipid needed to explore in the future. Therefore, we suggest that randomized clinical trials need to assess the effect of statins in CKD patients with normal serum lipid. Whether statins can be prescribed for aiming to inhibit inflammation in CKD also needed further study. Trial Registration. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022310334.

Background and Aim: Vascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD.Methods: Embase, the Cochrane Central Register of Controlled Trials, and Medline were searched from inception until November 15, 2021. The terms exercise, CKD, dialysis, kidney transplant, and randomized controlled trial (RCT) were searched alone or in combination. RCTs were included when studies compared exercise with active control, usual care, or no intervention, and the studies reported vascular function on patients with CKD.Results: This meta-analysis included 18 RCTs with 817 patients. Exercise training was significantly associated with decreased pulse wave velocity weighted mean difference (WMD), −0.56; 95% confidence interval (CI), −1.02 to −0.09, P = 0.02 and augmentation index (WMD, −3.26; 95% CI, −5.46 to −1.05, P = 0.004). It was also significantly associated with improved peak VO2 (WMD, 2.64; 95% CI, 1.94–3.35, P < 0.00001), general health (WMD, 7.03; 95% CI, 0.65–13.42, P = 0.03), and vitality (WMD, 9.1; 95% CI, 2.50–15.69, P = 0.007).Conclusions: The meta-analysis suggested that exercise training improved vascular function in patients with CKD. An exercise program should be considered as one of the management strategies for vascular dysfunction in patients with CKD. Further studies are needed to demonstrate that exercise training improves cardiovascular diseases in patients with CKD.

Acute kidney injury (AKI), a common condition associated with a high mortality rate, is characterized by declined glomerular filtration rate, retention of nitrogen products, and disturbances in balance of water, electrolyte, and acid-base. Up to date, there is no effective treatment for AKI. Despite the continuous improvement in blood purification techniques, a considerable proportion of patients with AKI still progress to end-stage renal disease. These patients with advanced stage of end-stage renal disease will require long-term renal replacement therapy, which places a heavy burden on the family and the society. In recent years, the use of traditional Chinese medicine (TCM) in AKI management has been gradually increasing. Clinical evidence has demonstrated that three-month treatment with TCM produced better clinical outcomes in terms of clinical effectiveness rate and improvement in renal function (serum creatinine, neutrophil gelatinase-associated lipocalin, and cystatin C) compared with Western medicine. Rhubarb is a commonly used herb in TCM for the treatment of AKI. The main active component of rhubarb is emodin, which was first recorded in Shennong’s Classic of Materia Medica. It has been shown that emodin has a variety of pharmacological activities including antibacterial, anti-inflammatory, antiulcer, and immunosuppressive effects. Emodin has been found to be effective against renal fibrosis and has been widely studied for its effects on kidney diseases such as diabetic nephropathy, renal fibrosis, and AKI. Moreover, promising results have been obtained from these studies. In this study, the results obtained from research on the use of emodin for AKI treatment has been reviewed.