OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Objective To investigate the composition ratios and trends of different etiologies after liver biopsy for patients with unexplained liver diseases.Methods A retrospective analysis was performed for the etiology of 960 patients with unexplained liver diseases who were hospitalized and underwent liver biopsy in The Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2020,and the etiologies were categorized by year and age group.The chi-square test was used for comparison of categorical data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.Results There was a tendency of increase in the overall composition ratio of unexplained liver diseases over the past decade.The leading diagnosis after liver biopsy was autoimmune liver disease(AILD)in 306 patients(31.9%),followed by nonalcoholic fatty liver disease(NAFLD)in 95 patients(9.9%)and drug-induced liver disease(DILI)in 82 patients(8.5%),and there were still 320 patients with undetermined causes(33.3%).There were significant differences in sex ratio and median age distribution between the patients with different etiologies(sex ratio:χ2=155.36,P<0.001;median age distribution:H=182.48,P<0.001).AILD had been the leading etiology in 2011-2020,and there was a tendency of reduction in the composition ratio of AILD(χ2=24.40,P<0.001).NAFLD accounted for the highest proportion of 17.6%in the adolescent stage,while AILD accounted for the highest proportion of 17.8%,47.3%,and 56.3%,respectively,in the young,middle-aged,and elderly stages.Conclusion There is a tendency of increase in the composition ratio of unexplained liver diseases in patients undergoing liver biopsy,with AILD being the main disease diagnosed after liver biopsy,followed by NAFLD and DILI,but one-third of the patients still have an unclear etiological diagnosis.

Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To explore the influence of injection methods of different contrast agents on CMR image quality,and further optimize"one-stop"examination process under the premise of the analysis for high-pressure bolus pressure curve of contrast-enhanced(CE)cardiac magnetic resonance(CMR).Methods:The data of CMR examination of 70 patients with old myocardial infarction who admitted to the department of emergency of Xuanwu Hospital,Capital Medical University from December 2023 to December 2024 were selected as research objects.They were divided into an observation group and a control group by a simple randomization method,with 35 cases in each group.The observation group adopted gadolinium contrast agent injection with double-phase double-flow,with two bolus injections at 4 ml/s and 2 ml/s sequentially.The control group adopted the injection with single-phase double-flow,with only one bolus injection at 4 ml/s.The dynamic pressure time curve was drawn,and the total bolus dose and pressure peak of two kinds of injection methods were compared.The residual liquid samples of the observation group and the control group were collected after injection of contrast agent was conducted.After the residual liquids of 10 ml,20 ml and 30 ml were derived respectively,the T1 mapping sequence was used to collect signal intensity values,and to compared the difference of that between two groups.The signal-to-noise ratio(SNR)of left ventricular blood pool,infarcted myocardium and distal myocardium,and the contrast-to-noise ratios(CNR)between infarcted myocardium and blood pool,and between distal myocardium and blood pool were compared between the observation group and the control group.Results:There was no statistical difference in the total dose of bolus injection between the observation group and the control group(P>0.05).The peak value of the pressure of bolus injection in the observation group and control group were respectively(87.4±11.3)pound force per square inch(PSI)and(104.0±20.1)PSI,and the difference was statistically significant(t=5.81,P<0.05).T1 signal intensity values of 10 ml residual liquid and 20 mL residual liquid were respectively 1984.43±70.26 and 2190.56±195.96 in observation group,and they were respectively 1203.36±184.99 and 2884.64±349.39 in control group,and the differences were significant(t=-3.57,6.03,P<0.05).The T1 signal intensity value of 30mL residual fluid sample was 4371.75±75.16 in observation group,and that was 4261.86±110.68 in control group,and the difference was no significant(P>0.05).The SNR value of blood pool was(4.88±1.01)in observation group,which was lower than(8.25±1.36)in control group,and the difference of that between two groups was significant(t=6.11,P<0.05).The CNR values of infarcted myocardium and blood pool,of remote myocardium and blood pool between two groups were statistically significant(t=-4.79,-5.39,P<0.05).Conclusion:The contrast agent of high-pressure bolus injection with dual-phase dual-flow method can not only explore the time window of the extravasation of contrast agent,but also improve the SNR and the CNR of CMR images,and further optimize the CMR examination process.

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Objective:To explore the influence of injection methods of different contrast agents on CMR image quality,and further optimize"one-stop"examination process under the premise of the analysis for high-pressure bolus pressure curve of contrast-enhanced(CE)cardiac magnetic resonance(CMR).Methods:The data of CMR examination of 70 patients with old myocardial infarction who admitted to the department of emergency of Xuanwu Hospital,Capital Medical University from December 2023 to December 2024 were selected as research objects.They were divided into an observation group and a control group by a simple randomization method,with 35 cases in each group.The observation group adopted gadolinium contrast agent injection with double-phase double-flow,with two bolus injections at 4 ml/s and 2 ml/s sequentially.The control group adopted the injection with single-phase double-flow,with only one bolus injection at 4 ml/s.The dynamic pressure time curve was drawn,and the total bolus dose and pressure peak of two kinds of injection methods were compared.The residual liquid samples of the observation group and the control group were collected after injection of contrast agent was conducted.After the residual liquids of 10 ml,20 ml and 30 ml were derived respectively,the T1 mapping sequence was used to collect signal intensity values,and to compared the difference of that between two groups.The signal-to-noise ratio(SNR)of left ventricular blood pool,infarcted myocardium and distal myocardium,and the contrast-to-noise ratios(CNR)between infarcted myocardium and blood pool,and between distal myocardium and blood pool were compared between the observation group and the control group.Results:There was no statistical difference in the total dose of bolus injection between the observation group and the control group(P>0.05).The peak value of the pressure of bolus injection in the observation group and control group were respectively(87.4±11.3)pound force per square inch(PSI)and(104.0±20.1)PSI,and the difference was statistically significant(t=5.81,P<0.05).T1 signal intensity values of 10 ml residual liquid and 20 mL residual liquid were respectively 1984.43±70.26 and 2190.56±195.96 in observation group,and they were respectively 1203.36±184.99 and 2884.64±349.39 in control group,and the differences were significant(t=-3.57,6.03,P<0.05).The T1 signal intensity value of 30mL residual fluid sample was 4371.75±75.16 in observation group,and that was 4261.86±110.68 in control group,and the difference was no significant(P>0.05).The SNR value of blood pool was(4.88±1.01)in observation group,which was lower than(8.25±1.36)in control group,and the difference of that between two groups was significant(t=6.11,P<0.05).The CNR values of infarcted myocardium and blood pool,of remote myocardium and blood pool between two groups were statistically significant(t=-4.79,-5.39,P<0.05).Conclusion:The contrast agent of high-pressure bolus injection with dual-phase dual-flow method can not only explore the time window of the extravasation of contrast agent,but also improve the SNR and the CNR of CMR images,and further optimize the CMR examination process.