Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective To explore the value of functional magnetic resonance imaging(MRI)techniques,including intravoxel incoherent motion(IVIM),T1 mapping,and T2 mapping,in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction(IUGR).Methods An IUGR rat model was established through a low-protein diet during pregnancy.Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group,while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group(n=8 for each group).The apparent diffusion coefficient(ADC),true diffusion coefficient(Dt),pseudo-diffusion coefficient(D*),perfusion fraction(f),T1 value,and T2 value of the renal cortex and medulla were compared,along with serum creatinine and blood urea nitrogen levels among the groups.Results The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group,and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group(P＜0.05).The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group,and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group,with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group(P＜0.05).The T2 values in the renal medulla were higher than those in the cortex across all groups(P＜0.05).There were no significant differences in the T2 values of either the cortex or medulla among the groups(P＞0.05).There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups(P＞0.05).Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group,whereas glomerular atrophy,cystic stenosis,and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group.Conclusions IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats.MRI T1 mapping can be used to evaluate kidney damage in IUGR rats,and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.[Chinese Journal of Contemporary Pediatrics,2024,26(3):289-296]

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.
Humans ; Rhododendron/chemistry* ; Arthritis, Rheumatoid/drug therapy* ; Anti-Inflammatory Agents ; Diterpenes/pharmacology* ; Analgesics

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

OBJECTIVE: To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients. METHODS: Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups. RESULTS: The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01). CONCLUSIONS QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.
Humans ; Aged ; Arsenic/therapeutic use* ; Powders/therapeutic use* ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVES: To investigate the changes in the pathogen spectrum and antimicrobial resistance over time in neonatal sepsis. METHODS: The medical data were collected from the neonates who were diagnosed with sepsis in the Second Xiangya Hospital of Central South University from January 2010 to December 2019. The incidence rate of sepsis, the pathogen spectrum, and the characteristics of antimicrobial resistance were analyzed. RESULTS: The incidence rate of neonatal sepsis was 4.02% (447/11 111). The top four pathogens detected were coagulase-negative staphylococci (CoNS), Klebsiella pneumoniae, Escherichia coli, and Candida. The incidence rate of sepsis and the pathogen spectrum showed no significant changes over time. Klebsiella pneumoniae was the most frequent pathogen in preterm infants, very low birth weight infants, and small-for-gestational-age infants, accounting for 33.9%, 29.5%, and 42.5%, respectively. CoNS, Klebsiella pneumoniae, and Escherichia coli had a high resistance rate to penicillins and third-generation cephalosporins. CONCLUSIONS The incidence of neonatal sepsis is high, and the main pathogen is CoNS. The pathogens of neonatal sepsis have a high resistance rate to penicillins and third-generation cephalosporins. It is recommended to enhance the prevention and control of neonatal infection, strengthen the surveillance of pathogens, and further standardize the rational use of antibiotics.
Infant ; Infant, Newborn ; Humans ; Neonatal Sepsis/etiology* ; Anti-Bacterial Agents/therapeutic use* ; Microbial Sensitivity Tests ; Retrospective Studies ; Drug Resistance, Bacterial ; Infant, Premature ; Sepsis/complications* ; Escherichia coli ; Cephalosporins ; Penicillins

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.
Aged ; Atrial Fibrillation/complications* ; Blood Glucose/analysis* ; Fasting ; Humans ; Male ; Middle Aged ; Prospective Studies ; Thromboembolism/etiology*

OBJECTIVES: To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR). METHODS: Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T ¹H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content. RESULTS: The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05). CONCLUSIONS Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.
Adult ; Animals ; Female ; Fetal Growth Retardation ; Gene Expression ; Humans ; Liver/metabolism* ; Organic Chemicals ; Pregnancy ; RNA, Messenger/metabolism* ; Rats

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA₂DS₂-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.
Adult ; Aged ; Atrial Fibrillation/surgery* ; Catheter Ablation ; Feasibility Studies ; Heart Septal Defects, Atrial ; Humans ; Male ; Middle Aged ; Punctures ; Radiofrequency Ablation ; Stroke Volume ; Ventricular Function, Left

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.
Animals ; Drugs, Chinese Herbal/toxicity* ; Fruit ; Gardenia ; Liver ; Proteomics ; Rats ; Signal Transduction