This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To investigate the relationship between uric acid metabolism and brain injury following cardiopulmonary bypass(CPB)in rats.Methods Healthy male SD rats were randomly assigned to either a Sham group or a CPB group,each comprising 12 rats.The Sham group only underwent vascular puncture and did not perform CPB conversion,while the CPB group was subjected to a CPB procedure with a perfusion duration of 110 min,and the brain tissue was collected post-procedure.Microdialysate was collected 1 h before and after CPB initiation.Apoptosis in the paraventricular nucleus(PVN)was assessed using TUNEL staining,and the expression of Bax mRNA in cerebral cortex and hypothalamus was determined via real-time quantitative PCR.Apoptosis-related protein expression was analyzed by Western blotting.Differentially expressed genes(DEGs)were identified through RNA-sequencing between brain tissues of two groups,and Gene Ontology(GO)analysis was performed to identify enriched pathways among the DEGs.Protein-protein interaction(PPI)networks were constructed using String and Cytoscape softwares to identify key genes.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was employed to analyze differential metabolites in the PVN before and after CPB,with Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis constructed subsequently.Uric acid levels in the hypothalamus was measured using a uric acid assay kit,and the expression of key enzymes of uric acid metabolism[xanthine reductase(XDH),adenosine deaminase(ADA)]and uric acid transporter[organic anion transporter family protein 1(OAT1),organic anion transporter family protein 3(OAT3),ATP-binding cassette transporter subfamily G member 2(ABCG2),glucose transporter 9(GLUT9)]genes in the hypothalamus was evaluated by real-time quantitative PCR.Results Real-time quantitative PCR revealed a significant upregulation of Bax mRNA in the cerebral cortex and hypothalamus of CPB group compared to Sham group(P<0.05).TUNEL staining indicated a significantly higher apoptosis rate of cells in PVN region in CPB group than that in Sham group(19.0%±5.0%vs.7.6%±0.8%,P=0.01).Western blotting showed a significantly increased Bcl-2/Bax ratio in the hypothalamus of CPB group compared to Sham group(P<0.05).A total of 2829 DEGs were identified between Sham group and CPB group,with 1374 upregulated genes and 1455 downregulated genes.Uric acid metabolism-related pathways were predominantly enriched in purine nucleoside metabolism and biosynthesis,purine nucleoside monophosphate metabolism,purine nucleoside triphosphate metabolism,purine ribonucleotide metabolism and biosynthesis,purine ribonucleoside monophosphate metabolism and biosynthesis,purine ribonucleoside triphosphate metabolism and biosynthesis,and reaction to purine compounds.Eighteen differential metabolites were identified in the microdialysate,with 13 upregulated and 5 downregulated metabolites.KEGG enrichment analysis identified 7 significantly enriched metabolic pathways,among which the nicotinate and nicotinamide metabolism pathways were closely related to uric acid metabolism.Both RNA-sequencing and LC-MS/MS analysis suggested alterations in uric acid metabolism in CPB groups.Post-CPB,uric acid concentration in the hypothalamic tissue significantly increased(P<0.01),and the expression of XDH and ADA mRNA in the hypothalamus were significantly increased(P<0.05),while the expression of ABCG2,OAT1,OAT3 and GLUT9 mRNA significantly decreased(P<0.001).Conclusion Uric acid metabolism in brain is altered during CPB,which may be an important mechanism for brain injury following CPB.

Objective To explore the diagnosis and clinical characteristics of atypical severe pneumonia caused by Chlamydia abortus(C.abortus).Methods Clinical data of 4 patients diagnosed with atypical severe pneumonia caused by C.abortus in a hospital from January 2021 to November 2022 were collected.Clinical characteristics,dia-gnosis and treatment,and precautions of the disease were comprehensively analyzed.Results All 4 patients were male,aged 63-73 years old,with acute onset,high fever,cough and expectoration.Three patients had a history of contact with poultry,one patient had a history of contact with abortion goat.The interval between the emerging of clinical symptoms and the onset of acute respiratory failure in 4 patients was 1-6 days,and the oxygenation index(PaO2/FiO2)at admission was less than 200 mmHg,which gradually decreased with the progression of the disease,active support with a ventilator was necessary.Two patients had an increase in white blood cell count,4 had an in-crease in neutrophil percentage,3 had a mild decrease in platelet count.Among 4 patients,2,2,3 and 4 patients showed elevated levels of aspartate aminotransferase,alanine aminotransferase,creatine kinase,and serum creati-nine respectively,2 patients had mild hyponatremia,4 patients showed significant increase in C-reactive protein,procalcitonin,and interleukin-6 levels.Four patients'chest CT findings showed main involvement of single or mul-tiple lung lobes,with exudation and consolidation,and later involvement of multiple lobes of lung.The metageno-mic next-generation sequencing of bronchoalveolar lavage fluid detected the DNA sequence of C.abortus.Based on the clinical manifestations,contact history,chest CT,and metagenomic next-generation sequencing results of 4 pa-tients,the diagnosis was C.abortus.atypical severe pneumonia.After timely adjustment of the treatment of anti-in-fection regimen based on doxycycline,the patients'condition improved and were discharged.Conclusion C.abor-tus may also cause human pneumonia,which can lead to serious clinical outcome after infection.Patient had a histo-ry of animal contact should be alert to such diseases.Metagenomic next-generation sequencing can detect C.abortus.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Phosphatidylinositol 4 kinases are the initial and key molecules of the phosphatidyl inositol signaling pathway.Among them,the phosphatidylinositol 4-kinaseⅢ β(PI4KⅢβ)is in-volved in the synthesis of the Golgi PI4P pool,playing a vital role in numerous physiological processes.Meanwhile,the en-zyme is an important host factor mediating the replication of some pathogenic RNA viruses,and participating in other patho-logical processes such as bacterial infection and malaria.In ad-dition,studies have shown that the function of PI4KⅢβ is regu-lated by numerous factors,including host and viral protein bind-ing partners.This review will discuss the structure and the phys-iopathology regulatory mechanism of PI4KⅢβ.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.