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

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

OBJECTIVE: To investigate the prognostic value of ¹⁸ F-deoxyglucose (FDG) PET/CT metabolic parameters combined with clinicopathological features for newly diagnosed diffuse large B-cell lymphoma (DLBCL) before treatment, and analyze the relationship between tumor metabolic volume (MTV), total lesion glycolysis (TLG) and clinicopathological features. METHODS: The clinical data of 120 patients with pathologically confirmed DLBCL were retrospectively analyzed and ¹⁸F-FDG PET/CT was performed 1 week before treatment. The metabolic parameters including SUVmax, SUVmean, tumor-to-blood standardized uptake value ratio (TBR), tumor-to-liver standardized uptake value ratio (TLR) were obtained. MTV and TLG of the lesions were obtained with 41% of SUVmax as the threshold, and the correlation of MTV and TLG with clinicopathological features were analyzed. Progression-free survival (PFS) was calculated by follow-up for 6-153 months. Receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier test, log-rank test and Cox proportional hazards model were used to analyze the date. RESULTS: The optimum cut-off values of the SUVmax, MTV, TLG, TBR and TLR for predicting tumor progression were 22.25, 256.05, 5 232.67, 12.97 and 10.60, respectively. The patients were divided into two groups according to the above cut-off values, respectively. Kaplan-Meier survival analysis showed that there were statistically significant differences in PFS between the two group (all P <0.05). The MTV and TLG values were correlated with NCCN-IPI score, Ann Arbor stage, serum lactate dehydrogenase level, and C-MYC, BCL-2, BCL-6 gene rearrangement (all P <0.05). Univariate analysis showed that NCCN-IPI score >3, C-MYC, BCL-2, BCL-6 gene rearrangement positive, SUVmax≥22.25, MTV≥256.05 cm³, TLG≥5 232.67 g and TBR≥12.97 were adverse factors for prognosis (HR: 1.949-5.759, all P <0.05). Multivariate Cox regression analysis showed that C-MYC, BCL-2 gene rearrangement positive and TLG≥5 232.67 g were all independent risk factors affecting PFS (HR: 4.660, 3.350, 4.031, all P <0.05). CONCLUSION The ¹⁸F-FDG PET/CT metabolic parameters SUVmax, MTV, TLG, TBR and TLR can be used as important indicators to predict PFS of DLBCL patients, and combining clinicopathological features can better predict the prognosis of patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

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

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

The importance of evaluating the oxygen supply system of the medical aircraft was introduced.With considerations on the characteristics of the oxygen supply system of the medical aircraft during its development and application,an oxygen supply system effectiveness evaluation method was proposed based on the analytic hierarchy process and the experience of experts in the field of medical aircraft,which involved in seven evaluation indexes of total oxygen supply,pipeline airtight-ness,single-nozzle flow adjustment characteristics,single-nozzle outlet pressure adjustment characteristics,disassembly and assembly,mechanical operation and fixation ability.The effectiveness evaluation method proposed was of significance for accurately grasping the changes in the performance of the oxygen supply system.References were provided for the ground maintenance of the oxygen supply system of the medical aircraft.[Chinese Medical Equipment Journal,2024,45(1):89-92]

Objective To explore the effect of barretinib on mice with acute lung injury(ALI)by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The male C57BL/6 mice were randomly divided into control group,model group and experimental-L,-M-H groups.Except for the control group,the other four groups were constructed ALI models by intraperitoneal injection of lipopolysaccharide.The control and model groups were given equal volume 0.9％NaCl by gavage.The experimental-H,-M,-L groups were administered with 1.00,0.50 and 0.25 mg·mL-1 barretinib solution 200 μL by gavage.Five groups were treated for 48 hours with once every 12 hours.The levels of inflammatory cytokine in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay.The expression levels of Occludin,JAK2 and STAT3 in mouse lung tissue were detected by Western blot.Results The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid for experimental-M,-H groups,model group and control group were(228.48±25.41),(198.53±23.11),(317.32±32.85)and(48.93±2.59)ng·L-1;the levels of interleukin-6 were(118.81±14.85),(98.58±13.82),(172.23±25.94)and(49.47±3.06)ng·L-1;the relative expression levels of Occludin were 0.48±0.13,0.49±0.11,0.28±0.09 and 0.69±0.21;the phospho-JAK2/JAK2 ratios were 0.51±0.13,0.32±0.09,0.75±0.21 and 0.16±0.05;the phospho-STAT3/STAT3 ratios were 0.43±0.11,0.27±0.08,0.78±0.21 and 0.17±0.05,respectively.The differences of above indicators were statistically significant between the experimental-M,-H groups,control group and model group(all P＜0.05).Conclusion Barretinib can reduce the lung inflammatory response and improves the level of tight junction protein in lung tissue to protect ALI mice by inhibiting the JAK2/STAT3 signaling pathway.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective:To investigate the expression of NOD-like receptor protein 3(NLRP3)inflammasome and its relation-ship with granulosa cell apoptosis in patients with polycystic ovary syndrome(PCOS).Methods:Follicular fluid and ovarian granulosa cells were collected from 17 PCOS patients(PCOS group)and 20 non-PCOS patients(control group),and the expression levels of pro-inflammatory factor,TNF-α,IL-1β and IL-18 in follicular fluid were detected by ELISA.RT-PCR and Western blot were used to de-tect NLRP3 mRNA and NLRP3 inflammasome associated protein NLRP3,ASC and cleaved caspase-1 and autophagy related protein LC3-Ⅱ/LC3-Ⅰ and p62 expression level in granulosa cells.TUNEL assay was used to detect the apoptotic level of granulosa cells in both groups.NLRP3 silenced siRNA(si-NLRP3)and negative control sequence(si-NC)were transfected into human ovarian cancer granulosa cell line KGN cells by siRNA interference technique in vitro.TNF-α was used to simulate PCOS-related cell damage.KGN cells were divided into 4 groups according to different treatment methods:Ctrl group,TNF-α group,TNF-α+si-NLRP3 group and TNF-α+si-NC group.The levels of DHEA,testosterone,IL-1β and IL-18 in supernatant were detected by ELISA.TUNEL assay was used to detect the apoptosis level of KGN cells.The LC3-Ⅱ/LC3-Ⅰ and p62,NLRP3,ASC and cleaved caspase-1 protein expression levels,and NF-κB p-p65 level(NF-κB p-p65/NF-κB p65)in KGN cells were detected by Western blot.Results:Compared with con-trol group,the concentration of TNF-α,IL-1β,and IL-18 in follicular fluid of PCOS patients,and LC3-Ⅱ/LC3-Ⅰ,NLRP3 mRNA and the protein expression of NLRP3,ASC,and cleaved caspase-1 in granulosa cells of and apoptosis were significantly increased(P<0.05 or P<0.01),while the protein expression of p62 was significantly decreased(P<0.01).Compared with Ctrl group,the levels of DHEA,testosterone,IL-1β and IL-18 in supernatant of TNF-α group,TNF-α+si-NC group,and TNF-α+si-NLRP3 group,and LC3-Ⅱ/LC3-Ⅰ,ASC and cleaved caspase-1 protein expression,and the level of NF-κB p-p65 and apoptosis were significantly increased(P<0.05 or P<0.01),while p62 protein was significantly decreased(P<0.01).NLRP3 was significantly decreased except in TNF-α+si-NLRP3 group(P<0.01),while in the TNF-α group and TNF-α+si-NC group was significantly increased(P<0.01).However,com-pared with TNF-α group,the above indexes in TNF-α+si-NLRP3 group were significantly decreased(P<0.05),and TNF-α+si-NC group had no significant change(P>0.05).Conclusion:The over-activated NLRP3 inflammasome in granulosa cells may promote cell inflammatory injury and autophagy apoptosis in PCOS patients through NF-κB pathway.