Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

A nomogram model of spectral CT quantitative parameters and clinical characteristics predicting lymphovascular invasion of gastric cancer.

Objective: The study established a nomogram based on quantitative parameters of spectral computed tomography (CT) and clinical characteristics, aiming to evaluate its predictive value for preoperative lymphovascular invasion (LVI) in gastric cancer (GC). Methods: From December 2019 to December 2021, 171 patients with pathologically confirmed GC were retrospectively collected with corresponding clinical data and spectral CT quantitative data. Patients were divided into LVI-positive and LVI-negative groups based on their pathological results. The univariate and multivariate logistic regression analyses were used to identify the risk factors and construct a nomogram. The calibration curve and receiver operating characteristic (ROC) curve were adopted to evaluate the predictive accuracy of nomogram. Results: Four clinical characteristics or spectral CT quantitative parameters, including Borrmann classification (P = 0.039), CA724 (P = 0.007), tumor thickness (P = 0.031), and iodine concentration in the venous phase (VIC) (P = 0.004) were identified as independent factors for LVI in GC patients. The nomogram was established based on the four factors, which had a potent predictive accuracy in the training, internal validation and external validation cohorts, with the area under the ROC curve (AUC) of 0.864 (95% CI, 0.798-0.930), 0.964 (95% CI, 0.903-1.000) and 0.877 (95% CI, 0.759-0.996), respectively. Conclusion: This study constructed a comprehensive nomogram consisting spectral CT quantitative parameters and clinical characteristics of GC, which exhibited a robust efficiency in predicting LVI in GC patients.

Protein Nanotubes as Advanced Material Platforms and Delivery Systems.

Protein nanotubes (PNTs) as state-of-the-art nanocarriers are promising for various potential applications both in the food and pharmaceutical industries. Derived from edible starting sources like α-lactalbumin, lysozyme, and ovalbumin, PNTs bear properties of biocompatibility and biodegradability. Their large specific surface area and hydrophobic core facilitate chemical modification and loading of bioactive substances, respectively. Moreover, their enhanced permeability and penetration ability across biological barriers such as intestinal mucus, extracellular matrix, and thrombus clot, make it promising platforms for health-related applications. Most importantly, their simple preparation processes enable large-scale production, supporting applications in the biomedical and nanotechnological fields. Understanding the self-assembly principles is crucial for controlling their morphology, size, and shape, and thus provides the ground to a multitude of applications. Here, the current state-of-the-art of PNTs including their building materials, physicochemical properties, and self-assembly mechanisms are comprehensively reviewed. The advantages and limitations, as well as challenges and prospects for their successful applications in biomaterial and pharmaceutical sectors are then discussed and highlighted. Potential cytotoxicity of PNTs and the need of regulations as critical factors for enabling in vivo applications are also highlighted. In the end, a brief summary and future prospects for PNTs as advanced platforms and delivery systems are included.

The association between maternal urinary Bisphenol A levels and neurodevelopment at age 2 years in Chinese boys and girls: A prospective cohort study.

The impact of maternal exposure to Bisphenol A on child cognitive development as well as its sex dimorphism remains uncertain. This study used data of 215 mothers and their children from a birth cohort in Shanghai. Urinary BPA were measured in spot urine samples of mothers at late pregnancy and children at age 2 years. Cognitive development was evaluated by Ages & Stages Questionnaires, Third Edition (ASQ-3) at age 2 years. Urinary BPA was detectable in 98.9% of mothers (geometric mean, GM: 2.6 µg/g. creatinine) and 99.8% children (GM: 3.4 µg/g. creatinine). Relative to the low and medium BPA tertiles, high tertile of maternal urinary BPA concentrations were associated with 4.8 points lower (95% CI: -8.3, -1.2) in gross motor and 3.7 points lower (95% CI: -7.4, -0.1) in problem-solving domain in girls only, with adjustment for maternal age, maternal education, pre-pregnancy BMI, passive smoking during pregnancy, parity, delivery mode, birth-weight for gestational age, child age at ASQ-3 test. This negative association remained with additional adjustment for child urinary BPA concentrations at age 2 years. No association was observed in boys. These results suggested the sex-dimorphism on the associations of maternal BPA exposure with gross motor and problem-solving domains in children at age 2 years. This study also indicated that optimal early child development should start with a healthy BPA-free "in utero" environment.

N-3 PUFA Deficiency Aggravates Streptozotocin-Induced Pancreatic Injury in Mice but Dietary Supplementation with DHA/EPA Protects the Pancreas via Suppressing Inflammation, Oxidative Stress and Apoptosis.

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.

Effect of Serum Ferritin on the Prognosis of Patients with Sepsis: Data from the MIMIC-IV Database.

Background: The present study aimed to investigate the prognostic value of serum ferritin in critically ill patients with sepsis by using the MIMIC-IV database. Methods: Data were extracted from the MIMIC-IV database. Adult patients who met the sepsis-3 criteria and had the test of ferritin were included. Patients were divided into subgroups according to the initial serum ferritin. The association between initial serum ferritin and in-hospital mortality was performed by using Lowessregression, logistic regression, and ROC analysis. Subgroup analysis was used to search for the interacting factors and verify the robustness of the results. Results: Analysis of the 2,451 patients revealed a positive linear relationship between serum ferritin and in-hospital mortality. Patients with high-ferritin had a higher risk of in-hospital mortality, but no significant association was found in the low-ferritin subgroup compared with those whose ferritin was in the normal reference range. Serum ferritin had moderate predictive power for in-hospital mortality (AUC = 0.651), with an optimal cut-off value of 591.5 ng/ml. Ferritin ≥591.5 ng/ml acted as an independent prognostic predictor of in-hospital mortality, which increased the risk of in-hospital mortality by 119%. Our findings were still robust in subgroup analysis, and acute kidney injury and anemia were considered interactive factors. Conclusion: High-level serum ferritin was an independent prognostic marker for the prediction of mortality in patients with sepsis. Further high-quality research is needed to confirm the relationship between ferritin and the prognosis of septic patients.

Selective and replicable neuroimaging-based indicators of pain discriminability.

Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1-3, total N = 366) and two fMRI (Datasets 4-5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability.

Research progress on effects of traditional Chinese medicine on myocardial ischemia-reperfusion injury: A review.

Ischemic heart disease (IHD) is a high-risk disease in the middle-aged and elderly population. The ischemic heart may be further damaged after reperfusion therapy with percutaneous coronary intervention (PCI) and other methods, namely, myocardial ischemia-reperfusion injury (MIRI), which further affects revascularization and hinders patient rehabilitation. Therefore, the investigation of new therapies against MIRI has drawn great global attention. Within the long history of the prevention and treatment of MIRI, traditional Chinese medicine (TCM) has increasingly been recognized by the scientific community for its multi-component and multi-target effects. These multi-target effects provide a conspicuous advantage to the anti-MIRI of TCM to overcome the shortcomings of single-component drugs, thereby pointing toward a novel avenue for the treatment of MIRI. However, very few reviews have summarized the currently available anti-MIRI of TCM. Therefore, a systematic data mining of TCM for protecting against MIRI will certainly accelerate the processes of drug discovery and help to identify safe candidates with synergistic formulations. The present review aims to describe TCM-based research in MIRI treatment through electronic retrieval of articles, patents, and ethnopharmacology documents. This review reported the progress of research on the active ingredients, efficacy, and underlying mechanism of anti-MIRI in TCM and TCM formulas, provided scientific support to the clinical use of TCM in the treatment of MIRI, and revealed the corresponding clinical significance and development prospects of TCM in treating MIRI.

Downregulation of PDCD4 by deSUMOylation associates with the progression of gestational trophoblastic disease.

INTRODUCTION: Gestational trophoblastic disease (GTD) encompasses a range of trophoblastic disorders from hydatidiform mole (HM), to malignant gestational trophoblastic neoplasia (GTN). The exact molecular mechanisms of GTN remain unknown. Dysregulation and dysfunction of programmed cell death 4 (PDCD4)have been observed in many cancers. The roles of PDCD4 in GTD have not been previously reported. METHODS: A total of 161 cases of formalin-fixed, paraffin-embedded trophoblast blocks, and 36 cases of fresh trophoblast tissues were collected, including normal first trimester placentas, HM, and invasive HM. Choriocarcinoma cells JAR and JEG-3 were employed. The expressions of PDCD4 and small ubiquitin-like modifier 2/3 (SUMO2/3) were examined by immunohistochemistry, quantitative reverse transcription PCR and Western blotting in trophoblastic tissues and cells. The relationship between SUMOylation and PDCD4 was investigated. The effects of PDCD4 on proliferation, invasion, and migration of choriocarcinoma cells were evaluated by Cell Counting Kit-8 and transwell assays post siRNA transfection. Extracellular Matrix & Adhesion Profiler PCR Array was used to screen the downstream molecules of PDCD4. RESULTS: PDCD4 was significantly repressed in HM tissues. Loss of PDCD4 expression was demonstrated in 90% invasive HMs. Choriocarcinoma cells also displayed with suppressed PDCD4 expression. The varied expression of PDCD4 was paralleled by SUMO2/3. Inhibition of SUMOylation reduced the expression of PDCD4. Silencing of PDCD4promoted proliferation/migration/invasion, upregulatedMMP3/MMP8/ITGB2, and downregulated TIMP1/TIMP2 in choriocarcinoma cells. DISCUSSION: Our results suggest that reduced SUMOylation is one reason for suppressed PDCD4 in GTD. Loss of PDCD4 likely determines the malignant phenotype of GTN by dysregulating some members of the MMPs/TIMPs/integrins complex.

Stress signaler p38 mitogen-activated kinase activation: a cause for concern?

Oxidative stress (OS) induced activation of p38 mitogen-activated kinase (MAPK) and cell fate from p38 signaling was tested using the human fetal membrane's amnion epithelial cells (AEC). We created p38 KO AEC using the CRISPR/Cas9 approach and tested cell fate in response to OS on an AEC-free fetal membrane extracellular matrix (ECM). Screening using image CyTOF indicated OS causing epithelial-mesenchymal transition (EMT). Further testing revealed p38 deficiency prevented AEC senescence, EMT, cell migration, and inflammation. To functionally validate in vitro findings, fetal membrane-specific conditional KO (cKO) mice were developed by injecting Cre-recombinase encoded exosomes intra-amniotically into p38αloxP/loxP mice. Amnion membranes from p38 cKO mice had reduced senescence, EMT, and increased anti-inflammatory IL-10 compared with WT animals. Our study suggested that overwhelming activation of p38 in response to OS inducing risk exposures can have an adverse impact on cells, cause cell invasion, inflammation, and ECM degradation detrimental to tissue homeostasis.

Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients: A Retrospective Observational Study.

OBJECTIVE: To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older. METHODS: This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression. RESULTS: Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19. CONCLUSION: The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

6-Shogaol alleviates CCl4-induced liver fibrosis by attenuating inflammatory response in mice through the NF-κB pathway.

Liver fibrosis is a global health problem caused by a number of diseases related to liver damage. 6-Shogaol is a biologically active substance derived from the rhizome of Zingiber officinale Roscoe with anti-tumor, anti-inflammatory, and antioxidant properties. To explore the effects of 6-Shogaol on liver fibrosis, we used a mouse model of the condition in which mice were injected intraperitoneally with carbon tetrachloride (CCl4) at a dose of 2 mL/kg three times per week for a period of 4 weeks. 6-Shogaol was administered orally at two different doses (5 mg/kg, 20 mg/kg) 30 min before CCl4 injection. CCl4 induced severe liver injury and fibrosis, as indicated by significant inflammatory cell infiltration, disordered liver structure, increased activities of aspartate aminotransferase and alanine aminotransferase (liver damage markers) in serum, elevated collagen deposition, and overexpressed alpha-smooth muscle actin (α-SMA, marker of hepatic stellate cells activation) in liver tissues, whereas 6-Shogaol administration rescued those alterations dose-dependently. We found that 6-Shogaol suppressed CCl4-induced inflammatory response by inhibiting macrophage recruitment, release of pro-inflammatory factors, and activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in liver tissues. Additionally, we demonstrated that 6-Shogaol blocked CCl4-induced activation of the nuclear factor-kappa B (NF-κB) pathway, which is a vital transcriptional regulator of the inflammatory response. Altogether, this study demonstrates that 6-Shogaol can prevent CCl4-induced liver fibrosis by suppressing inflammatory response through the NF-κB pathway and suggests that 6-Shogaol can be used for liver fibrosis prevention.

Hypoxic effects on the mitochondrial content and functions of the placenta in fetal growth restriction.

INTRODUCTION: In this study we examined the hypothesis that a hypoxic intrauterine environment causes mitochondrial dysfunction of trophoblasts in fetal growth restriction (FGR). METHODS: The mtDNA content, mRNA levels of mitochondrial encoded genes (ND6, COX I), mitochondrial membrane proteins (COX I, COX IV and VDAC), HIF-1α and BINP3 (mitophagy receptor) protein levels were examined in FGR placentas and normal placentas. The mitochondrial function (ATP production and mitochondrial membrane potential-ΔΨm) and above related proteins were further examined in hypoxic HTR-8/SVneo cells induced by cobalt chloride (CoCl2). Mitophagy and its regulating mechanism under hypoxia in FGR was also investigated. RESULTS: Compared with normal controls, both FGR placentas and CoCl2-treated trophoblast cells demonstrated statistically lower mtDNA content, reduced mRNAs of mitochondrial encoding genes, and decreased mitochondrial membrane proteins, accompanied by increased HIF-1α. Mitochondrial functions were impaired as demonstrated by decreased ATP production, and, reduced ΔΨm in CoCl2-treated cells. Meanwhile, mitophagy was markedly enhanced as indicated by increased LC3 fluorescent puncta in mitochondria of hypoxic trophoblastic cells. The upregulated BINP3 expression was demonstrated in FGR placentas as well as in hypoxic trophoblastic cells. DISCUSSION: We demonstrated that hypoxic conditions lead to impaired mitochondrial function in trophoblasts in FGR. Reduced mtDNA may be associated with enhanced mitophagy via activating HIF-1α/BINP3 signalling pathway, that may, in turn, affect nutrition and energy transfer to the growth-restricted fetus.

Efficacy and safety of regorafenib or fruquintinib plus camrelizumab in patients with microsatellite stable and/or proficient mismatch repair metastatic colorectal cancer: an observational pilot study.

This study was to investigate the efficacy and safety of regorafenib or fruquintinib combined with camrelizumab in patients with microsatellite stable (MSS) and/or proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC). Medical records of MSS/pMMR mCRC patients who received regorafenib (80 mg) or fruquintinib (3 mg) once a day (21 days on/7 days off) plus camrelizumab (200 mg) every three weeks in Yuhuangding Hospital between January 2020 and June 2020 were retrospectively collected. Follow-up data up to November 1st, 2020 was gathered. The primary endpoint was the objective response rate (ORR) and disease control rate (DCR). The safety profile was the secondary endpoint. A total of 16 patients were enrolled. The ORR was 25.0% (4/16) and the DCR was 62.5% (10/16). The main adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (81.3%), fatigue (43.8%), hypertension (37.5%), hand-foot skin reaction (25.0%), and thyroid dysfunction (25.0%). Most AEs were grade 1 or 2, with only 1 patient of grade 3 liver dysfunction. All the AEs were ameliorated by effective symptomatic treatment. Regorafenib or fruquintinib plus camrelizumab exhibited promising efficacy in patients with MSS/pMMR mCRC. The toxicity was moderate and manageable.

Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice.

Sea cucumbers are widely consumed in traditional medicine and food. Sea cucumbers-derived sulfated sterol exhibits a sulfate group at C-3 position, which is different from phytosterol with a hydroxyl group. However, the effect of sterol sulfate on metabolic syndrome remains unknown. The purpose of the present study is to investigate the alleviation of sterol sulfate on high-fat-high-fructose diet (HFFD)-induced insulin resistance and inflammation. After 2 weeks feeding with HFFD, male C57BL/6J mice were continuously fed with HFFD plus 0.4 % (w/w) sterol sulfate or phytosterol for 6 weeks. The OGTT was carried out at 7 weeks. At the end of the experimental period, the changes of glycogen, circulating glucose, insulin, pro-inflammatory cytokine and adiponectin were measured. H&E staining was used to observe the morphological changes in adipose tissue. Furthermore, the underlying molecular mechanisms were investigated. Dietary sterol sulfate was superior to phytosterol in reducing body weight gain, adipocyte hypertrophy, and levels of circulating glucose and insulin, as well as increasing the glycogen content of tissues. Furthermore, sterol sulfate ameliorated insulin resistance mainly due to the inhibition of gluconeogenesis, the promotion of glycogen synthesis and GLUT4 translocation by activating PI3K/Akt signaling pathway. Additionally, sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release. Sterol sulfate exhibited a more significant effect than phytosterol in alleviating HFFD -induced insulin resistance and inflammation, which might be closely related to the sulfate group. The results might provide insights into the prevention and alleviation of metabolic syndrome.

The pathogenesis and treatment in antineutrophil cytoplasmic antibody associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a systemic autoimmune disease characterized by leukocytoclastic inflammation of small blood vessels. Commonly detected autoantibodies include anti-protease 3 (PR3) and anti-myeloperoxidase (MPO). Although cell necrosis plays an important role in the production of autoantibodies and the pathogenesis of AAV, the correlation between their titers and disease activity remains elusive. As improved detection techniques facilitate early diagnosis, a satisfactory efficacy can be achieved in patients with mild to medium severe AAV treated with glucocorticoids and immunosuppressants. However, resistant and relapsing AAV, sometimes life-threatening, do exist in clinical practice. In-depth understanding of pathogenesis of AAV may lend novel insight into the mechanism responsible for its formation and help find effective targeted therapies for refractory patients.

Destrin Contributes to Lung Adenocarcinoma Progression by Activating Wnt/ß-Catenin Signaling Pathway.

Lung cancer, especially lung adenocarcinoma, is one of the most common neoplasms worldwide. However, the mechanisms underlying its initiation, development, and metastasis are still poorly understood. Destrin (DSTN) is a member of ADF/cofilin family. Its detailed biological function remains unknown, although it is reported that DSTN is involved in cytoskeleton remodeling and regulation of actin filament turnover. Recent evidence has shown that high expression of cofilin-1 is associated with invasion and poor prognosis of several types of human tumors, but the detailed mechanism is still entirely unclear, particularly in lung cancer tumorigenesis and malignancy. Here, we report that DSTN was highly expressed in a mouse lung cancer model induced by urethane and in clinical lung adenocarcinoma tissue samples. Its expression level was positively correlated with cancer development, as well as metastasis to the liver and lymph nodes. Consistently, it was directly associated with the poor prognosis of lung adenocarcinoma patients. Furthermore, we also found that DSTN promotes cell proliferation, invasion, and migration in vitro, and facilitates subcutaneous tumor formation and lung metastasis via intravenous injection in vivo. Mechanically, DSTN associates with and facilitates nuclear translocation of ß-catenin, which promotes epithelial-to-mesenchymal transition (EMT). Taken together, our results indicated that DSTN enhances lung cancer malignancy through facilitating ß-catenin nuclear translocation and inducing EMT. Combined with multivariate analyses, DSTN might potentially serve as a therapeutic target and an independent prognostic marker of lung adenocarcinoma. IMPLICATIONS: This finding indicates that DSTN facilitates ß-catenin nuclear translocation and promotes malignancy in lung adenocarcinoma.

Efficacy and safety of azithromycin combined with glucocorticoid on refractory Mycoplasma pneumoniae pneumonia in children: A PRISMA-compliant systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of azithromycin (AZI) combined with glucocorticoid (GC) in the treatment of children with refractory Mycoplasma pneumoniae. METHODS: Computer search for PubMed, EMbase, Cochrane Library, China Biomedical Literature Database (CBMdisc), China Knowledge Network (CNKI), Wanfang, VIP (VIP), and a randomized controlled trial (RCT) of AZI combined with GC in the treatment of children with refractory Mycoplasma pneumoniae pneumonia test (RCT), the search time limit is built until March 20, 2019. Two researchers independently performed literature screening, data extraction, and literature risk bias, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 RCTs were included, including 1130 patients. Meta-analysis showed that AZI combined with GC therapy significantly improved the total effective rate of the disease compared with the conventional treatment group (odds ratio [OR] = 6.37; 95% confidence interval [CI] 4.03, 10.07; P < .00001; I = 0%), effectively shortened the antipyretic time (SMD = -2.29; 95% CI -2.70, -1.88; P < .0001); promoted lung inflammation absorption (SMD = -1.89; 95% CI -2.38, -1.40; P < .0001), reduced cough time (SMD = -2.39; 95% CI -2.80, -1.99; P < .0001); shortened hospital stay (SMD = -2.19; 95% CI -3.21, -1.17; P < .0001); improved imaging findings (OR = 5.38; 95% CI 1.09, 26.51, P = .04); reduced inflammation index (SMD = -3.15; 95% CI -4.93, -1.36; P = .004); improved immune function (SMD = 1.29; 95% CI -0.02, 2.60; P < .0001); had no significant adverse reactions (OR = 1.18; 95% CI 0.71, 1.98; P = .53). CONCLUSIONS: According to the current limited research evidence, the addition of GCs to the conventional treatment of refractory Mycoplasma pneumoniae in children can improve the clinical efficacy to a certain extent, and the safety is better. However, due to the quality and quantity of the included literature, the conclusions of this study need to be confirmed by more high-quality studies.

De novo Synthesis of SAA1 in the Placenta Participates in Parturition.

Serum amyloid A1 (SAA1) is an acute phase protein produced mainly by the liver to participate in immunomodulation in both sterile and non-sterile inflammation. However, non-hepatic tissues can also synthesize SAA1. It remains to be determined whether SAA1 synthesized locally in the placenta participates in parturition via eliciting inflammatory reactions. In this study, we investigated this issue by using human placenta and a mouse model. We found that SAA1 mRNA and protein were present in human placental villous trophoblasts, which was increased upon syncytialization as well as treatments with lipopolysaccharides (LPS), tumor necrosis factor-α (TNF-α), and cortisol. Moreover, significant increases in SAA1 abundance were observed in the placental tissue or in the maternal blood in spontaneous deliveries without infection at term and in preterm birth with histological chorioamnionitis. Serum amyloid A1 treatment significantly increased parturition-pertinent inflammatory gene expression including interleukin-1ß (IL-1ß), IL-8, TNF-α, and cyclooxygenase-2 (COX-2), along with increased PGF2α production in syncytiotrophoblasts. Mouse study showed that SAA1 was present in the placental junctional zone and yolk sac membrane, which was increased following intraperitoneal administration of LPS. Intraperitoneal injection of SAA1 not only induced preterm birth but also increased the abundance of IL-1ß, TNF-α, and COX-2 in the mouse placenta. Conclusively, SAA1 can be synthesized in the human placenta, which is increased upon trophoblast syncytialization. Parturition is accompanied with increased SAA1 abundance in the placenta. Serum amyloid A1 may participate in parturition in the presence and absence of infection by inducing the expression of inflammatory genes in the placenta.