-
Heliyon Aug 2023To analyze the efficacy and safety of proprietary Chinese medicines for the treatment of Lupus Nephritis (LN) based on the reticulated meta analysis. The study aim to... (Review)
Review
OBJECTIVE
To analyze the efficacy and safety of proprietary Chinese medicines for the treatment of Lupus Nephritis (LN) based on the reticulated meta analysis. The study aim to provide evidence-based evidence for the clinical treatment of LN.
METHODS
The studies related to the randomized controlled studies (RCTs) on the treatment of LN with oral proprietary Chinese medicines were obtained from China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), SinoMed, Wanfang, PubMed, Web of Science, Embase and Cochrane Library databases since its inception-August 2022. Cochrane tools were used for risk bias assessment, Stata 13.0 and ADDIS 1.16.5 software were used for net evidence analysis.Results.1) 41 RCTs with 3124 L N patients were included, involving 9 types of proprietary Chinese medicines.2) The meta-analysis showed that in terms of efficacy, the top 3 Chinese patent medicine interventions were Xin Gan Bao Capsule (XGB) +western medicines (WM), Huang Kui Capsule (HK) + WM, Kun Xian Capsule (KX) + WM; in terms of reducing adverse event rate, the top 3 Chinese patent medicine interventions were Yi Shen Hua Shi Granules (YSHS) + WM, Jin Shui Bao Capsule (JSB) + WM, HK + WM; in terms of reducing 24 h urine protein, the top 3 Chinese patent medicine interventions were XGB + WM, YSHS + WM, Bai Ling Capsule (BL) + WM; in terms of reducing blood creatinine (Cr), the top 3 Chinese patent medicine interventions were Yi Shen Granules (YS) + WM, JSB + WM, KX + WM; in terms of reducing urea nitrogen (BUN), the top 3 Chinese patent medicine interventions were Shen Kang Capsule (SK) + WM, HK + WM, JSB + WM; in terms of reducing systemic lupus erythematosus disease activity index (SLEDAI) scores, the top 3 Chinese patent medicine interventions were JSB + WM, BL + WM, YSHS + WM; in terms of improving complement C3, the top 3 Chinese patent medicine interventions were HK + WM, XGB + WM, BL + WM; in terms of improving complement C4, the top 3 Chinese patent medicine interventions were KX + WM, YSHS + WM, BL + WM.
CONCLUSION
Xin Gan Bao Capsule has a good efficacy in improving efficiency and the level of complement C3, lowering 24 h urine protein. Jin Shui Bao Capsule and Huang Kui Capsule have a good efficacy in treating LN. However, more multicentre, large sample and high quality RCTs are needed for validation the results.
PubMed: 37593598
DOI: 10.1016/j.heliyon.2023.e18711 -
Clinical Medicine Insights. Oncology 2022A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM...
BACKGROUND
A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM.
METHODS
A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ test and the Mann-Whitney -test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively.
RESULTS
The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 10/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM.
CONCLUSION
Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.
PubMed: 35250324
DOI: 10.1177/11795549221079171 -
Pain and Therapy Mar 2022Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments....
INTRODUCTION
Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions.
METHODS
Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of > 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC).
RESULTS
The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 + 0.148 × lymphocyte + (-0.001) × bodily pain indicators of SF-36 + (-0.001) × pregabalin dose + 0.028 × LDLC + 0.001 × C4 + (-0.508) × sex + (-0.128) × stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively.
CONCLUSIONS
Seven factors were significantly associated with poor PRF outcome: male sex, advanced stage of HZ, higher pregabalin dose, higher bodily pain indicators of SF-36, and lower lymphocyte count, LDLC, and complement C4 in the peripheral blood. PRF should be applied to patients with ZAP as early as possible to achieve satisfactory outcomes.
PubMed: 35094299
DOI: 10.1007/s40122-022-00355-3 -
Frontiers in Immunology 2020Vitamin D and complement components shared some common pathophysiological pathways in the musculoskeletal system, circulation, and metabolism, which were linked to...
Vitamin D and complement components shared some common pathophysiological pathways in the musculoskeletal system, circulation, and metabolism, which were linked to physical function. It is hypothesized that serum complement components may interact with vitamin D in respect of the physical activities of daily living (PADLs). To investigate if serum complement components 3 (C3), complement components 4 (C4), and 25-hydroxyvitamin D [25(OH)D] associate with PADLs, and to examine whether the association between 25(OH)D levels and PADLs varies at different complement component levels among Chinese centenarians. This study was conducted in a group of population-based centenarians. PADLs were evaluated using the Barthel Index. Multiple regressions were used to analyze the associations among 25(OH)D, complements C3 and C4, and PADLs. Among 943 participants, 672 (71.3%) had physical dependence (PD). After adjusting for potential confounders, serum 25(OH)D and C3 levels were positively correlated with PADLs, while C4 levels were negatively correlated with PADLs (s < 0.05). Serum 25(OH)D levels significantly interacted with both C3 ( for interaction = 0.033) and C4 ( for interaction = 0.006) levels on PADLs. At lower complement component levels, the multivariate odds ratios (ORs) of the upper tertile of vitamin D for PD were 0.32 (95% CI: 0.18-0.55) in the C3 group and 0.29 (95% CI: 0.16-0.50) in the C4 group. At higher complement component levels, the ORs in the C3 and C4 groups were not statistically significant. In a group of population-based Chinese centenarians, we observed that serum complement C3 and 25(OH)D levels were positively associated with PADLs, while C4 was negatively associated with PADLs. The associations between 25(OH)D levels and PADLs were more pronounced in groups with lower serum complement component levels.
Topics: Activities of Daily Living; Aged, 80 and over; Biomarkers; China; Complement C3; Complement C4; Complement System Proteins; Exercise; Female; Humans; Longevity; Male; Public Health Surveillance; Vitamin D
PubMed: 32765534
DOI: 10.3389/fimmu.2020.01543 -
Translational Psychiatry Sep 2021Structural variation in the complement 4 gene (C4) confers genetic risk for schizophrenia. The variation includes numbers of the increased C4A copy number, which...
Structural variation in the complement 4 gene (C4) confers genetic risk for schizophrenia. The variation includes numbers of the increased C4A copy number, which predicts increased C4A mRNA expression. C4-anaphylatoxin (C4-ana) is a C4 protein fragment released upon C4 protein activation that has the potential to change the blood-brain barrier (BBB). We hypothesized that elevated plasma levels of C4-ana occur in individuals with schizophrenia (iSCZ). Blood was collected from 15 iSCZ with illness duration < 5 years and from 14 healthy controls (HC). Plasma C4-ana was measured by radioimmunoassay. Other complement activation products C3-ana, C5-ana, and terminal complement complex (TCC) were also measured. Digital-droplet PCR was used to determine C4 gene structural variation state. Recombinant C4-ana was added to primary brain endothelial cells (BEC) and permeability was measured in vitro. C4-ana concentration was elevated in plasma from iSCZ compared to HC (mean = 654 ± 16 ng/mL, 557 ± 94 respectively, p = 0.01). The patients also carried more copies of the C4AL gene and demonstrated a positive correlation between plasma C4-ana concentrations and C4A gene copy number. Furthermore, C4-ana increased the permeability of a monolayer of BEC in vitro. Our findings are consistent with a specific role for C4A protein in schizophrenia and raise the possibility that its activation product, C4-ana, increases BBB permeability. Exploratory analyses suggest the novel hypothesis that the relationship between C4-ana levels and C4A gene copy number could also be altered in iSCZ, suggesting an interaction with unknown genetic and/or environmental risk factors.
Topics: Complement C4; Complement C4a; Endothelial Cells; Genetic Predisposition to Disease; Humans; Schizophrenia
PubMed: 34552056
DOI: 10.1038/s41398-021-01583-5 -
International Journal of Molecular... Feb 2023Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by...
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants. Elevated baseline CRP at disease onset of AAV has already been described as a determinant of poor long-term outcomes. However, its clinical implications at disease onset of AAV, with respect to vasculitis manifestations and complement system activation that might also affect long-term outcomes, remain elusive. CRP levels were retrospectively analyzed in 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis; a total of 138 disease controls were also evaluated. Univariate and multivariate regression analysis was performed on clinicopathological parameters associated with CRP levels in ANCA-associated renal vasculitis. Results: Compared to disease controls, CRP elevation was common in ANCA-associated renal vasculitis and associated with de novo disease ( = 0.0169), critical illness ( = 0.0346), and severe deterioration of kidney function ( = 0.0167), independent of extrarenal disease manifestations. As confirmed by multiple regression analysis, CRP levels were correlated with active lesions predominated by interstitial arteritis in renal vasculitis, specifically with MPO-ANCA seropositivity ( = 0.0017). Based on analysis of systemic complement system activation and intrarenal complement deposits, CRP elevation was correlated specifically with complement C4 deposits in interstitial arteries in the subgroup with myeloperoxidase (MPO)-ANCA seropositivity ( 0.039). Finally, this association was independent of systemic complement system activation, as reflected by the consumption of respective complement components. Here, we expand our current understanding of CRP in ANCA-associated renal vasculitis not only as an inflammatory marker, but potentially also as being involved in the pathogenesis of kidney injury by interaction with the complement system.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Arteritis; C-Reactive Protein; Complement C4; Kidney; Peroxidase; Retrospective Studies
PubMed: 36834488
DOI: 10.3390/ijms24043072 -
Lupus Jan 2023The severity of lupus nephritis (LN) varies between different ethnicities. However, there are limited data regarding disease severity for LN in patients from the Arabian... (Review)
Review
INTRODUCTION
The severity of lupus nephritis (LN) varies between different ethnicities. However, there are limited data regarding disease severity for LN in patients from the Arabian Gulf region; moreover, there are no treatment guidelines developed specifically for this population. The objective of this review was to characterise the incidence of LN, current treatment practices, the severity of LN, and the pathophysiology and biomarkers associated with LN in the Arabian Gulf region.
METHODS
A literature search using EMBASE was conducted in October, 2021 to identify publications reporting on the incidence, treatment practices, severity, pathophysiology or biomarkers associated with LN, from countries in the Arabian Gulf region (including Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates). Additional relevant publications were provided by collaborators. A manual review of the publications was conducted to determine their relevance and data on the outcomes of interest were extracted.
RESULTS
Of 3705 publications, 54 publications were identified as relevant. LN is one of the most commonly diagnosed renal diseases within the Arabian Gulf and approximately 10%-36% of all renal biopsies are for LN. Treatment patterns within the region appear to vary and generally follow treatment guidelines recommended by the Asia Pacific League of Associations for Rheumatology (APLAR), the European Alliance of Associations for Rheumatology (EULAR) and Kidney Disease Improving Global Outcomes (KDIGO). The majority of patients receive cyclophosphamide for induction therapy, whilst others receive mycophenolate mofetil. Most studies showed that the most frequently diagnosed class of LN within the Arabian Gulf region was Class IV (up to 63% of patients with LN). Sustained or increased levels of serum creatinine and proteinuria; and depressed levels of complement C3/C4 were commonly seen among patients with LN from the Arabian Gulf region.
CONCLUSIONS
This review identified that LN may manifest more severely among patients from the Arabian Gulf region than in other populations, such as Caucasian populations. A greater understanding of LN and the treatment practices within the region, as well as the development of more specific treatment guidelines for this population may help improve outcomes for patients with LN in the Arabian Gulf region.
Topics: Humans; Lupus Nephritis; Lupus Erythematosus, Systemic; Saudi Arabia; Bahrain; Kuwait; Complement C4
PubMed: 36331103
DOI: 10.1177/09612033221137248 -
Nephron 2020Antibody-mediated rejection (ABMR) in organ transplantation has been recognized as the main cause of graft rejection. Binding of donor-specific HLA antibody (DSA) and... (Review)
Review
Antibody-mediated rejection (ABMR) in organ transplantation has been recognized as the main cause of graft rejection. Binding of donor-specific HLA antibody (DSA) and A/B blood type antibody on graft endothelial cells causes complement-dependent tissue damage. C4d, a product of the complement cascade, has long been an indicator of graft tissue damage in graft endothelial cells. By contrast, recent evidences indicated histological findings of ABMR without C4d deposition in many cases and Banff classification criteria included a category of C4d-negative ABMR. Several mechanisms have been proposed for complement-independent tissue injury in the presence of DSA. It is well known that activated monocytes and macrophages infiltrate into graft tissues. The inflammatory environment triggered by the binding of DSA to endothelial cells alone can induce an allo-reaction of CD4 T-cells via graft endothelial cell HLA-class II. Accommodation is a condition that no rejections occur even in the presence of an antibody against donor organs and becomes attracting considerable attention as a therapeutic strategy to acquire long-term survival of the transplanted organs. Several recent publications have suggested some mechanistic insights about graft accommodation, including the upregulation of antioxidant, anti-apoptotic, and complement regulatory proteins genes via activation of PI3K/AKT survival signal or inactivation of extracellular signal-regulated protein kinase pro-inflammatory signals after DSA and anti-A/B antibody ligation on endothelial cells.
Topics: Complement C4b; Endothelial Cells; Graft Rejection; HLA Antigens; Humans; Isoantibodies; Organ Transplantation; Peptide Fragments; Tissue Donors
PubMed: 33238285
DOI: 10.1159/000510747 -
International Journal of Molecular... Mar 2015Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is... (Review)
Review
Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014) Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word "AFE" was searched singularly and associated individually to each of the other keywords. Of the 146 sources found, only 19 were considered appropriate for the purpose of this paper. The clinical course is characterized by a rapid onset of symptoms, which include: acute hypotension and/or cardiac arrest, acute hypoxia (with dyspnoea, cyanosis and/or respiratory arrest), coagulopathies (disseminated intravascular coagulation and/or severe hemorrhage), coma and seizures. The pathology still determines a significant morbidity and mortality and potential permanent neurological sequelae for surviving patients. At this moment, numerous aspects involving the pathophysiology and clinical development are still not understood and several hypotheses have been formulated, in particular the possible role of anaphylaxis and complement. Moreover, the detection of serum tryptase and complement components and the evaluation of fetal antigens can explain several aspects of immune response.
Topics: Animals; Complement C3; Complement C4; Embolism, Amniotic Fluid; Female; Humans; Immunohistochemistry; Mast Cells; Pregnancy; Tryptases
PubMed: 25807263
DOI: 10.3390/ijms16036557 -
Transplant International : Official... Apr 2015ABO-incompatible kidney transplantation is nowadays a well-established procedure to expand living donor transplantation to blood group incompatible donor/recipient... (Review)
Review
ABO-incompatible kidney transplantation is nowadays a well-established procedure to expand living donor transplantation to blood group incompatible donor/recipient constellations. In the last two decades, transplantation protocols evolved to more specific isohaemagglutinin elimination techniques and established competent antirejection protection protocols without the need of splenectomy. ABOi kidney transplantation associated accommodation despite isohaemagglutinin reappearance, C4d positivity of peritubular capillaries as well as the increased incidence of bleeding complications is currently under intense investigation. However, most recent data show excellent graft survival rates equivalent to ABO-compatible kidney transplantation outcome.
Topics: ABO Blood-Group System; Clinical Protocols; Complement C4; Graft Rejection; Hemagglutinins; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Kidney Transplantation; Rituximab; Transplantation Immunology
PubMed: 25387763
DOI: 10.1111/tri.12485