ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Objective To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide(FeNO)and conventional ventilatory lung function parameters in diagnosing bronchial asthma(referred to as"asthma")in children.Methods A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group,and 85 healthy children undergoing routine health checks as the control group.The study compared the differences in serum 14-3-3β protein concentrations between the two groups,analyzed the correlation of serum 14-3-3β protein with clinical indices,and evaluated the diagnostic efficacy of combining 14-3-3β protein,FeNO,and conventional ventilatory lung function parameters for asthma in children.Results The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group(P<0.001).Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E,and a negative correlation with conventional ventilatory lung function parameters(P<0.05).Cross-validation of combined indices showed that the combination of 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume had an area under the curve of 0.948 for predicting asthma,with a sensitivity and specificity of 88.9%and 93.7%,respectively,demonstrating good diagnostic efficacy(P<0.001).The model had the best extrapolation.Conclusions The combination of serum 14-3-3β protein,FeNO,and the percentage of predicted value of forced expiratory flow at 75%of lung volume can significantly improve the diagnostic efficacy for asthma in children.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Objective:To investigate the clinical outcome after surgery and first 131I treatment in patients with moderate-risk papillary thyroid cancer (PTC), and analyze the relevant factors that affect the therapeutic effect. Methods:From January 2018 to April 2019, 135 patients (48 males, 87 females; age (42.7±11.1) years) with moderate-risk PTC in the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into excellent response (ER) group, inderteriminate response (IDR) group, biochemical incomplete response (BIR) group and structural incomplete response (SIR) group, of which IDR, BIR, SIR were collectively referred to as the non-ER group. χ2 test and Mann-Whitney U test were used to compare the general clinical features between the ER and non-ER groups, and then multivariate logistic regression analysis was performed. The predicted value of pre-ablation stimulated thyroglobulin (ps-Tg) to ER was assessed by ROC curve analysis. Results:The treatment responses of 94 patients were ER, and those of 41 were non-ER. The differences in tumor size (0.80(0.50, 1.10) vs 1.00(0.55, 1.50) cm; U=1 491.50, P=0.036), the number of metastatic lymph nodes (3(2, 5) vs 4(2, 12); U=1 422.00, P=0.015), metastatic lymph node size (0.50(0.30, 0.65) vs 0.50(0.30, 1.45) cm; U=1 396.50, P=0.013), metastatic lymph node involvement rate (50%(30%, 70%) vs 60%(50%, 85%); U=1 441.50, P=0.024), metastatic lymph node location (central/lateral: 76/18 vs 24/17; χ2=7.40, P=0.007) and ps-Tg level (2.1(0.8, 5.3) vs 14.0(3.2, 35.2) μg/L; U=680.00, P<0.001) were statistically significant between the ER and non-ER groups. Multivariate logistic regression analysis showed that ps-Tg (odds ratio ( OR)=1.200, 95% CI: 1.107-1.302, P<0.001) was an independent factor influencing ER. The cut-off value of ps-Tg for predicting ER was 7.38 μg/L, with the sensitivity and specificity of 68.3%(28/41) and 87.2%(82/94) respectively. Conclusion:Moderate-risk PTC patients with smaller tumor size, fewer metastatic lymph nodes, lower metastatic lymph node involvement rate, metastatic lymph nodes in central area, smaller metastatic lymph node size, and ps-Tg<7.38 μg/L have better therapeutic effect after initial 131I treatment.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Objective:To summarize the clinical characteristics and risk factors of acute rejection(AR)of transplanted pancreas and kidney after simultaneous pancreas-kidney transplantation(SPK)and explore the effects of AR on the survival of transplanted pancreas, kidney and recipients.Methods:From September 2016 to July 2022, the relevant clinical data were retrospectively reviewed for 218 recipients undergoing SPK.According to whether or not AR occurred after SPK, they were assigned into two groups of AR(n=53)and non-AR(n=165). The relevant clinical data were compared for two groups of donors and recipients and the risk factors of AR analyzed by binary Logistic regression.Kaplan-Meier method was employed for comparing the survival rates of recipients/transplanted pancreas and kidneys in two groups.Results:A total of 53 cases(24.3%)developed ARs of transplanted pancreas(n=31, 14.2%)(5 of 2 ARs), transplanted kidney(n=15, 6.9%)(1 of 2 ARs)and transplanted pancreas & kidney AR(n=11, 5.0%)(2 of 2 ARs). Tacrolimus blood levels in AR and non-AR groups were(5.8±1.2)and(6.3±1.6)μg/L and failed to attain targets in 36(67.9%)and 78(47.3%)cases.During follow-ups, the incidence of pneumonia and urinary tract infections in AR group versus non-AR group were[43.4%(23/53)vs.27.3%(45/165)and 39.6%(21/53)vs.18.8%(31/165)]and the differences were statistically significant( P=0.028 & 0.002). The results of multifactorial regression analysis revealed that sub-optimal blood level of tacrolimus was an independent risk factor for an occurrence of AR in grafts of SPK recipients( OR=2.254, 95% CI: 1.167-4.353, P=0.016). Comparisons of 1/5-year postoperative survival rates between recipients in AR and no-AR group(98.1% vs.93.9% and 92.1% vs.92.4%)indicated that the differences were not statistically significant( P=0.233 & 0.806). Through comparing 1/5-year survival rates of transplanted pancreas in AR and non-AR groups(94.3% vs.100%, 89.4% vs.98.6%), the differences were statistically significant( P=0.003 & 0.004). And 1/5-year survival rates of transplanted kidneys in AR and non-AR groups(92.5% vs.100% and 90.2% vs.100%)were compared and the differences were statistically significant(all P<0.001). Conclusions:The incidence of AR is higher in transplanted pancreas and kidney after SPK.And the incidence of pneumonia and urinary tract infection is higher in AR group than that in non-AR group.Sub-optimal blood level of tacrolimus is an independent risk factor for the occurrence of AR.The 1/5-year survival rates of transplanted pancreas and transplanted kidney are lower in AR group than those in non-AR group.It has some effect on the survival of transplanted pancreas and kidney.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective To screen the targets of traditional Chinese medicine-derived potential plant molluscicides based on network pharmacology and explore the mechanisms of molluscicidal actions. Methods The traditional Chinese medicines with molluscicidal actions were screened based on retrospective literature reviews, and their molluscicidal efficiency was summarized. The active ingredients and potential targets of traditional Chinese medicines were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Unified Protein Database and literature mining using network pharmacology. The drug-active ingredient-target network was created using the software Cytoscape 3.7.2, and the key targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the Metascape software. Results A total of 27 types of snail control drugs derived from traditional Chinese medicines were screened from publications and classified into 14 categories. Network pharmacology identified 190 active ingredients, and the active ingredients with a high degree in the drug-active ingredient-target network included quercetin, linoleyl acetate, luteolin, beta-carotene, (24S)-ethylcholesta-5,22,25-trans-3beta-ol, fumarine and arctiin, with 181 corresponding potential targets screened. KEGG pathway enrichment analysis revealed that these targets were mainly located in 16 pathways, including the neuroactive ligand-receptor interactions, regulation of adipocyte lipolysis and adrenergic signal in myocardial cells. Conclusions This study preliminarily demonstrates the multi-ingredient, multi-target and multi-pathway mechanisms of action of 27 molluscicides. The screened key ingredient may provide the basis for isolation, purification and pharmacological studies of molluscicides, and the screened key targets and key pathways may facilitate the illustration of mechanisms of actions of traditional Chinese medicine-derived molluscicides and development of novel green molluscicides.