Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ² test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q₁, Q₃), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.
Humans ; Hyperaldosteronism/diagnosis* ; Nomograms ; Hypertension ; Cross-Sectional Studies ; Aldosterone ; Saline Solution ; Renin ; Potassium

Objective:To investigate the clinical effect of Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis in the treatment of qi deficiency, blood stasis and dampness and turbidity in chronic kidney disease (CKD) stage 5.Methods:Randomized controlled trial. A total of 102 elderly CKD stage 5 patients with Qi and Yin deficiency and turbid poison inherent type were selected from May 2021 to January 2022 of the Beijing Longfu Hospital. The patients were divided into two groups by random number table method. Control group (51 cases) received hemodialysis treatment for 4 weeks, and the observation group (51 cases) received Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis treatment for 4 weeks. The levels of BUN, SCr and β2-microglobulin (β2-MG), and K +, Ca 2+, P 3- content, hemoglobin were detected by automatic blood cell analyzer, and serum CRP and IL-6 levels were detected by latex enhanced immune scattering turbidimetry. The adverse reactions during the treatment and evaluate the clinical efficacy were observed and recorded. Results:During the treatment, 2 patients in the observation group withdrew from the study due to severe diarrhea, and other patients completed the study. There were significant differences in total response rate between observation group and control group [91.84%(45/49) vs. 74.51%(38/51); χ2=5.32, P=0.002]. After treatment, scores of lumbar and knee acerbity, tiredness and fatigue, edema, dizziness and tinnitus, fear of cold and warm, yellow face, dry stool and total score in observation group were significantly lower than those in the control group ( t=8.38, 13.44, 15.14, 13.09, 7.12, 7.73, 11.16, 11.45, P<0.01); the scores of SF-12-PCS and SF-12-MCS were significantly higher than those in the control group ( t=3.24, 4.22, P<0.01). After treatment, levels of serum BUN [(15.02±2.35)mmoL/L vs. (18.02±3.65)mmoL/L, t=4.87], SCr[(155.26±23.65) μmol/L vs. (184.49±35.49) μmol/L, t=4.83], β2-MG[(7.12±1.27)mg/L vs. (9.56±2.14)mg/L, t=6.90] and P 3-[(1.51±0.10) mmol/L vs. (2.02±0.19) mmol/L, t=16.70], K +[(3.65±0.54) mmol/L vs. (4.21±0.63)mmol/L, t=4.76] in observation group were significantly lower than those in the control group ( P<0.01); Ca 2+[(1.86±0.36)mmol/L vs. (2.35±0.42)mmol/L, t=6.25] was significantly higher than that of the control group ( P<0.01). No adverse reactions occurred during the treatment in the two groups ( P>0.05). Conclusion:Shenqi Dihuang Decoction and Xiaochengqi Decoction enema and hemodialysis can improve renal function, correct electrolyte disorder, reduce the level of inflammatory factors, improve the quality of life, and improve the therapeutic effect of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern.

This study aims to explore the improvement and the mechanism of the Alisma plantago-aquatica Linn. (ApL) on chronic glomerulonephritis (CGN). All animal experiments were followed the regulation of the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine. CGN mouse model was established by a single tail-vein injection of doxorubicin (Dox) (20 mg·kg^-1). One week after Dox administration, the mice received water extract of ApL (85 and 255 mg·kg^-1) by gavage once a day for 14 days. At the end of experiment, the urine albumin-to-creatinine ratio (ACR), serum albumin (ALB), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected, kidney histopathological H&E staining was analyzed. Active ingredients and action targets of ApL were collected from TCMSP database, and CGN-related targets were obtained from Genecards database. STRING platform was employed to perform protein-protein interaction (PPI), and Metascape platform was used for KEGG pathway and GO enrichment analysis. The results of experiments demonstrated that ApL (85 and 255 mg·kg^-1) could reduce the ACR and the content of SCr and BUN, and increase the content of ALB in mice. Network pharmacology results predicted that nuclear factor kappa-B (NF-κB)-related pathway and biological process of oxidoreductase activity regulation may be involved in the ApL-provided amelioration on CGN. The verification results showed that ApL could inhibit the activation of NF-κB and the expression of inflammatory factors in mice, and reduce the activity of renal myeloperoxidase (MPO). Meanwhile, ApL promoted the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream gene mRNA, and reduced the level of renal malondialdehyde (MDA) and reactive oxygen species (ROS), and further elevated renal glutathione (GSH) level. Based on network pharmacology combined experiments, this study found that ApL may improve CGN in mice through multiple targets and multiple pathways, in which the inhibition of NF-κB signaling and the activation of Nrf2 signaling may be important mechanisms involved.

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
Biomarkers/metabolism* ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Spermatozoa/metabolism*

A boy, aged 11 years, was admitted due to intermittent fever for 15 days, cough for 10 days, and "hemoptysis" for 7 days. The boy had fever and cough with left neck pain 15 days ago, and antibiotic treatment was effective. During the course of disease, the boy developed massive "hemoptysis" which caused shock. Fiberoptic bronchoscopy revealed a left pyriform sinus fistula with continuous bleeding. In combination with neck and vascular imaging examination results, the boy was diagnosed with internal jugular vein injury and thrombosis due to congenital pyriform sinus fistula infection and neck abscess. The boy was improved after treatment with temperature-controlled radiofrequency ablation for the closure of pyriform sinus fistula, and no recurrence was observed during the follow-up for one year and six months. No reports of massive hemorrhage and shock due to pyriform sinus fistula infection were found in the searched literature, and this article summarizes the clinical features, diagnosis, and treatment of this boy, so as to provide a reference for the early diagnosis of such disease and the prevention and treatment of its complications.
Abscess/surgery* ; Cough ; Fever/complications* ; Fistula/surgery* ; Hemoptysis/complications* ; Humans ; Male ; Neck ; Shock

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Stomach Neoplasms/genetics*

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.
Animals ; Autoimmune Diseases/therapy* ; Exosomes/metabolism* ; Immunomodulation ; Mesenchymal Stem Cells ; MicroRNAs/metabolism*

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Bundle-Branch Block/therapy* ; Cardiac Pacing, Artificial ; Cardiac Resynchronization Therapy ; Electrocardiography ; Humans ; Treatment Outcome