Validity of high resolution magnetic resonance imaging in detecting giant cell arteritis: a meta-analysis.

OBJECTIVES: This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques. METHODS: PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed. RESULTS: In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively. CONCLUSIONS: HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI. KEY POINTS: HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

Nephrotic-range proteinuria and central nervous involvement in typical hemolytic uremic syndrome: a case report.

BACKGROUND: Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs. CASE PRESENTATION: A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset. CONCLUSION: We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome.

[Effect of Glucocorticoid Pulse Therapy on Short-term Prognosis of Anti-neutrophil Cytoplasmic Antibodies-associated Glomerulonephritis].

Objective To investigate the prognosis predictors of anti-neutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis treated with glucocorticoid(GC).Methods The clinicopathological data of patients with biopsy-confirmed ANCA-associated glomerulonephritis were retrospective analyzed by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015. Pathological categories were re-classified. Renal remission rates,infection rates,and death events were compared between intravenous glucocorticoid(GC)pulse therapy group and non-pulse group. Logistic regression analysis was performed to analyze factors influencing the short-term prognosis.Results Among the 81 patients with ANCA-associated glomerulonephritis,49(60.5%)received GC pulse therapy and 32(39.5%)did not. The GC pulse group had significantly lower estimated glomerular filtration rate at baseline(eGFR0)than the non-pulse group(t=3.003,P=0.015)but significantly higher 24-hour urinary protein(24 hUP)(t=2.394,P=0.002)and Birmingham Systemic Vasculitis Activity Score(BVAS)(t=0.049,P=0.013). There was no significant difference in the cumulative amount of cyclophosphamide(CTX)(t=1.336,P=0.245)between these two groups. The overall renal remission rate of GC pulse group in the 6 th month was significantly lower(48.7% vs. 79.3%;χ 2=6.591,P=0.024). Univariate analysis showed that baseline 24 hUP(t=6.222,P=0.017),eGFR0(t=3.727,P=0.046),and pathological category(χ 2=7.654,P=0.045)were associated with the overall renal remission rate in the 6 th month. Multivariate analysis showed the crescent category was an independent factor(OR=20.63,95%CI:2.217-191.973,P=0.008;compared with sclerotic category)for overall renal remission rate in the 6 th month,while GC pulse therapy was not an predictor(OR=0.271,95%CI:0.062-1.179,P=0.082). A total of 37 patients experienced infections within 6 months. The infection rate in GC pulse group(55.1%,27/49)was significantly higher than that of non-pulse group(31.3%,10/32)(P=0.042). Univariate regression analysis showed that eGFR0(t=1.912,P=0.049),baseline BVAS(t=-3.360,P=0.001)and GC pulse(χ 2=6.249,P=0.014)were associated with infection events within 6 months. Multivariate analysis showed that the baseline BVAS was the only predictor with 1.089 times for every 1 point increase in BVAS(OR=1.089,95%CI:1.006-1.179,P=0.034). Conclusions Crescentic category favors renal remission independently compared with sclerotic category. Patients with crescentic category may benefit more from intensive treatment. BVAS acts as an independent risk factor of infection.

The renal manifestations of type 4 familial partial lipodystrophy: a case report and review of literature.

BACKGROUND: Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now. CASE PRESENTATION: A 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis and proteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novel heterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showed glomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopy results fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion. CONCLUSIONS: We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.

Fibronectin Glomerulopathy Caused by the Y973C Mutation in Fibronectin: A Case Report and Literature Review.

Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin. We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome. Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation. However, this mutation was not found in her parents. She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.

A Cohort Study of Incidences and Risk Factors for Thromboembolic Events in Patients with Idiopathic Membranous Nephropathy.

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ 2=18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy△.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm2) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m2 vs. -8.1±21.4 ml/min per 1.73 m2, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

[Mitophagy and nervous system disease].

Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.

[Role of mitophagy in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To investigate mitophagy in an animal model of hypoxic-ischemic brain damage (HIBD) and its role in HIBD. METHODS: A total of 120 neonatal Sprague-Dawley rats aged 7 days were divided into three groups: sham-operation, HIBD, and autophagy inhibitor intervention (3MA group). The rats in the HIBD group were treated with right common carotid artery ligation and then put in a hypoxic chamber (8% oxygen and 92% nitrogen) for 2.5 hours. Those in the 3MA group were given ligation and hypoxic treatment at 30 minutes after intraperitoneal injection of 2 µL 3MA. Those in the sham-operation group were not given ligation or hypoxic treatment. Single cell suspension was obtained from all groups after model establishment. Immunofluorescence localization was performed for mitochondria labeled with MitoTracker, autophagosomes labeled with LysoTracker, and autophagy labeled with LC3 to observe mitophagy. After staining with the fluorescent probe JC-1, flow cytometry was used to measure mitochondrial membrane potential. TTC staining was used to measure infarct volume. Cytoplasmic proteins in cortical neurons were extracted, and Western blot was used to measure the expression of mitophagy-related proteins. RESULTS: Compared with the sham-operation group, the HIBD group had a significant reduction in mitochondrial membrane potential (P<0.05), a significant increase in mitophagy (P<0.05), a significant increase in the expression of the proteins associated with the division of the mitochondrial Drp1 and Fis1 (P<0.05), and a significant reduction in the expression of the mitochondrial outer membrane protein Tom20 and the mitochondrial inner membrane protein Tim23 (P<0.05). Compared with the HIBD group, the 3MA group had a significantly greater reduction in mitochondrial membrane potential (P<0.05), but showed significantly reduced mitophagy (P<0.05). In addition, the 3MA group had a significantly increased degree of cerebral infarction compared with the HIBD group (P<0.05). CONCLUSIONS: HIBD can increase the degree of mitophagy, and the inhibition of mitophagy can aggravate HIBD in neonatal rats.

Influence and analysis of low-dosage steroid therapy in severe aristolochic acid nephropathy patients.

AIM: To investigate the effect of low-dosage steroid therapy in patients with severe aristolochic acid nephropathy (AAN). METHODS: Forty-three chronic AAN patients in the Peking Union Medical College Hospital and the First Affiliated Hospital of Xinxiang Medical College were included in this study from November 1998 to October 2013. According to the treatment method, the patients were divided into a steroid group (SG, n = 25) and a control group (CG, n = 18). The serum biochemical indicators at the basement in the two groups exhibited no obvious statistical differences. In comparison with the baseline data, the levels of serum creatinine at 3, 6, 9, and 12 months were analyzed. The blood pressure, haemoglobin, serum biochemical indicators, and the side-effects of steroid application were also observed. Urinary macrophage chemoattractant protein-1 (MCP-1) and transforming growth factor-1 (TGF-1) amounts were measured as well. RESULTS: (i) The serum creatinine content in the CG group was significantly higher than the baseline level during the follow-up(6, 9, and 12 months later), whereas in the SG group it decreased during the 3-6 month period and remained stable within 1 year. (ii) The biochemical indicators, blood pressure, and haemoglobin persisted stable. (iii) The side-effects of low-dosage steroid therapy were not severe and were tolerated by the AAN patients. (4) Urinary MCP-1 and TGF-1 concentrations were positively correlated with serum creatinine and decreased in the SG group. CONCLUSION: Low-dosage steroid therapy reversed or delayed the renal failure progression in severe chronic AAN patients, which may be associated with the suppression of MCP-1 and TGF-ß1 activities.

Clinical features of 30 patients with cryoglobulinemia.

OBJECTIVE: To summarize the clinical features of cryoglobulinemia. METHOD: We retrospectively analyzed the clinical data of 30 patients admitted to Peking Union Medical College Hospital from January 2003 to March 2013 due to cryoglobulinemia. RESULTS: The average age was(53.8±11.9)years in these 30 patients(12 men and 18 women),among whom 22 patient(73.3%)developed infectious diseases including hepatitis B(n=11)and hepatitis C(n=11);in addition,3 hepatitis B patients and 1 hepatitis C patient also had malignancies. Four patients(13.3%)were accompanied with malignant lymphocytic proliferation diseases,and three(10.0%)with connective tissue diseases. The cause of disease was unclear in 5 patients(16.7%). The clinical manifestations varied due to the primary diseases;notably,20 patients(66.7%)had an onset of purpura rash,22(73.3%)and 19(63.3%)were accompanied with hypertension and chronic renal insufficiency,respectively. The severity of renal involvement was relevant with the increase of C reactive protein,erythrocytes,sedimentation rate,and IgM and the decrease of complements. Treatment should be directed at the primary diseases. Glucocorticoid and immunosuppressants were good choices for relieving renal involvement. Elderly, type 1 cryoglobulinemia,and poor renal function were associated with the poor prognosis. CONCLUSIONS: Cryoglobulinemia is mainly seen in middle and elderly patients. It can often affect multiple systems,in particular the kidney. Inflammatory markers,IgM,and complements is related with the disease severity. Age,primary disease,and renal function are related with prognosis.

[Expression of calcineurin in podocytes in response to endoplasmic reticulum stress in diabetic nephropathy].

OBJECTIVE: To investigate the regulation of calcineurin (CaN) by endoplasmic reticulum stress (ERS) in podocytes in vitro and in vivo at the stage microalbuminuria in diabetic nehropathy (DN). METHODS: The urinary albumin excretions of C57BLKS/J (Lepr) db/db and db/m mice at the ages of 6, 9, and 12 weeks were measured. The expressions of CaN and synaptopodin of these mice were observed. In immortalized mouse podocytes, the expression of podocyte CaN incubated with different concentrations of paltimate was quantitatively determined by real-time PCR. The changes of CaN incubated with paltimate with or without ursodeoxy-cholic acid (UDCA) were analyzed by confocal microscopy and Western blotting. RESULTS: As urine protein increased, the expression of CaN was enhanced and the expression of synaptopodin was reduced in early stage DN db/db mice potocytes. In immortalized mouse podocytes, as the concentrations of palmitate increased, CaN mRNA increased. By confocal microscopy, the fluorescence intensity of CaN increased in palmitate treatment group. After co-incubation with palmitate and UDCA, the fluorescence intensity decreased. The similar results were shown by Western blotting. CONCLUSION: At the stage of microalbuminuria in DN, ERS in podocytes up-regulates the expression of CaN.

[Influence of Kudou Shencha decotion on INF-gamma, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats].

OBJECTIVE: To investigate the influence of Kudou Shencha decotion on INF-y, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats. METHOD: Forty Wistar male rats were divided into 5 groups randomly: Kudou Shencha decotion group with high dosage and low dosage, Qianleitai group, the model control group and normal group. The rat model of chronic nonbacterial prostatitis was established by multiple hypodermical injection of the suspension of prostatic protein purification with Freund's completed adjuvant. The level of intercellular adhesion molecule (ICAM-1), interferon gamma (INF-gamma) and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay (ELISA). RESULT: The content of ICAM-1 and MCP-1 in the model group was higher than that of the normal group (P < 0.05), the content of ICAM-1 was obviously decreased in Kudou Shencha decotion group with high dosage (P <0.05), the contents of MCP-1 were all obviously decreased in Kudou Shencha decotion groups and Qianlietai group. Compared with the model group, the contents of INF-gamma in all treatment groups were decreased insignificantly. CONCLUSION: Kudou Shencha decotion has the action of lowering the level of ICAM-1 and MCP-1, which may be one of the mechanisms of Kudou Shencha decotion in the therapy of chronic prostatitis.

To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study.

Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.

Lateral quadratus lumborum block vs acupuncture for postcesarean analgesia: a randomized clinical trial.

BACKGROUND: Improved pain control after cesarean section remains a challenging objective. Although both the lateral quadratus lumborum block (L-QLB) and acupuncture have been reported to provide superior postoperative analgesia after cesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of L-QLB and acupuncture following elective cesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton-term pregnancies scheduled for cesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or L-QLB group. L-QLB group received bilateral L-QLB with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy, and sham L-QLB. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 hours. Secondary endpoints included pain scores in the first 48 hours postoperatively, patient-controlled intravenous analgesia (PCIA) demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (interquartile range [range]) pain scores at 24 hours on movement were similar in patients receiving acupuncture or L-QLB (3 [2-4] vs 3 [2-4], respectively; P=.40). PCIA consumption and pain scores within 48 hours postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 hours postoperatively (P<.001), as well as shortened the time to first flatus (P=.03) and first drinking (P<.001) compared to L-QLB. In addition, the median time to mobilization in the L-QLB group was markedly prolonged compare with acupuncture group (17.0 [15.0-19.0] hours vs 15.3 [13.3-17.0] hours, estimated median difference, 1.5; 95% CI, 1-2; P<.001). CONCLUSION: As a component of multimodal analgesia regimen after cesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to L-QLB.

HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study.

Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30-1.84, P = 6.87 × 10-7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

The efficacy of vitamin D in treatment of fibromyalgia: a meta-analysis of randomized controlled studies and systematic review.

BACKGROUND AND AIMS: Recent studies have found potential benefits of vitamin D in relieving pain, and the results from randomized controlled trials of vitamin D for fibromyalgia have been promising. We conducted a comprehensive systematic review and meta-analysis to evaluate the efficacy of vitamin D for treating fibromyalgia. RESEARCH DESIGN AND METHODS: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for English-language articles. Based on the inclusion and exclusion criteria, we selected only randomized controlled studies that reported vitamin D versus placebo-controlled cure for fibromyalgia. After extracting valid data, a meta-analysis was performed using Stata 12.0. The major outcome in the pooled analysis was the Fibromyalgia Impact Questionnaire and Visual Analogue Scale (VAS) changes. RESULTS: Five studies including 315 participants were identified. These studies found that vitamin D was effective in reducing Fibromyalgia Impact Questionnaire scores compared with those of the control group, with significant differences (weighted mean difference = -7.82, 95% confidence interval: -12.05 to -3.59, P < 0.001). However, there was no statistical difference in VAS between the two groups (weighted mean difference = -0.60, 95% confidence interval: -1.38 to 0.17, P > 0.05). CONCLUSIONS: Vitamin D supplementation may be an effective fibromyalgia therapeutic approach.

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.

Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of recovering itself after injury. However, the hostile extrinsic microenvironment significantly hinders axon regeneration. Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration. Particularly, substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin (mTOR) signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries. In this review, we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury. Importantly, we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog (PTEN). Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway, we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose, and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination. To specifically tackle the blood-brain barrier issue, we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology. We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.

Effects of Motherwort Injection Versus Intramuscular Oxytocin for Preventing Postpartum Hemorrhage Among Women Who Underwent Cesarean Section.

Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.

Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome.

To determine whether Th17/Treg balance was abnormal in adult patients with minimal change nephrotic syndrome (MCNS), we studied 25 patients with new-onset MCNS and 20 normal persons. The results showed that MCNS patients exhibited a significant increase in Th17 number, Th17-related cytokines (IL-17 and IL-23), and transcription factor (RORγt) levels, as well as an obvious decrease in Treg number, Treg-related cytokines (TGF-ß1 and IL-10), and transcription factor (Foxp3) levels. The Th17/Treg ratios increased along with increased proteinuria and decreased albumin levels in patients with MCNS. IL-17 protein expression was also detected in the renal biopsy tissue of MCNS patients, particularly in patients with acute renal failure. Further, Th17/Treg balance returned to normal after effective corticosteroids therapy in 16 MCNS patients. These results indicated that Th17/Treg imbalance existed in MCNS patients, suggesting a potential role of Th17/Treg imbalance in the pathogenesis of MCNS.