OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

Objective To employ three dimensional high-resolution vessel wall magnetic resonance imaging(3D hr-VW-MRI)for analyzing the imaging characteristics of posterior circulation non-stenotic intracranial atherosclerotic plaque and to discuss its diagnostic value in identifying culprit plaques.Methods Ninety-three patients(age[62.94±9.70]years old,67 males,26 females)with non-stenotic atherosclerosis in our hospital from Jan.2019 to Jan.2021 were retrospectively recruited.The imaging features of plaques,including luminal area,maximum wall thickness and minimum wall thickness at the most stenotic site,stenosis rate,plaque burden,remodeling index,eccentricity index,enhancement ratio at the most stenotic site,and intraplaque hemorrhage,were measured based on T1-weighted imaging(T1WI)and contrast-enhanced T1WI.The culprit plaque was defined as a lesion arising from the responsible vascular supply area to a fresh infarction on the diffusion weighted imaging(DWI)and T2 fluid attenuated inversion recovery(T2-FLAIR)images with accompanying ischemic stroke/transient ischemic attack(TIA).A plaque was considered to be a nonculprit plaque when it occurred in patients with presumed ischemic stroke/TIA,but without an infarct on DWI and T2-FLAIR.Results Sixty-one culprit plaques and 32 non-culprit plaques were analyzed.The proportions of patients with hyperlipidemia,National Institutes of Health stroke scale(NIHSS)score,narrowest plaque enhancement rate,and incidence of intraplaque hemorrhage in the culprit plaque group were significantly higher than those in the non-culprit plaque group(all P＜0.05).Multivariate logistic regression analyses showed that NIHSS score(odds ratio[OR]=1.799,95％confidence interval[CI]1.303-2.484,P＜0.001),enhancement ratio(OR=1.076,95％CI 1.027-1.128,P=0.002)and intraplaque hemorrhage(OR=30.708,95％CI 2.563-367.925,P=0.007)were associated with plaque type.Conclusion NIHSS score,enhancement ratio at the most stenotic site,and intraplaque hemorrhage are independent risk factors for culprit plaques in patients with posterior circulation non-stenotic intracranial atherosclerotic disease.These indicators may help identify such culprit plaques and could be used to screen individuals with plaques having these characteristics,thereby providing a basis for early preventive interventions.

Objective To explore the value of oral contrast-enhanced ultrasonography (OCEUS) combined with contrast-enhanced CT in predicting preoperative T staging in patients with gastric cancer. Methods A retrospective analysis was conducted on 80 patients with gastric cancer confirmed via endoscopic biopsy or postoperative pathology at the First People’s Hospital of Jining from January 2021 to November 2024. The cohort included 56 males and 24 females, aged 38-79 years, with a median age of 55.9 years. All patients underwent both OCEUS and contrast-enhanced CT within one week prior to surgery. T staging of gastric cancer was determined using OCEUS, contrast-enhanced CT, or their combination. The results were compared with pathological T staging, and statistical differences in accuracy were analyzed. Results Pathological T staging identified T1 in 9 cases, T2 in 16 cases, T3 in 42 cases, and T4 in 13 cases. OCEUS indicated T1 in 6 cases, T2 in 14 cases, T3 in 50 cases, and T4 in 10 cases, with an accuracy rate of 80.0%. Contrast-enhanced CT indicated T1 in 4 cases, T2 in 12 cases, T3 in 52 cases, and T4 in 12 cases, with an accuracy rate of 75.0%. The combination of OCEUS and contrast-enhanced CT indicated T1 in 6 cases, T2 in 15 cases, T3 in 47 cases, and T4 in 12 cases, with an accuracy rate of 87.5%. The combined approach demonstrated significantly higher accuracy in preoperative T staging compared to either method alone (P < 0.05). Conclusion The combination of OCEUS and contrast-enhanced CT improves the accuracy of preoperative T staging in gastric cancer patients, providing valuable support for their diagnosis and treatment.

Objective:To investigate the effect of myo-inositol on the reactivation of ocular dominance plasticity in the visual cortex of adult mice and its mechanisms.Methods:Thirty-two male SPF-grade C57BL/6J mice at postnatal day 60 (P60) were randomly divided into four groups using a random number table: normal control group, monocular form deprivation (MD) group, myo-inositol group (myo-inositol administered to normal mice), and MD+ myo-inositol group (myo-inositol administered to MD mice), with 8 mice in each group.The right eyes of MD group and MD+ myo-inositol group received MD on P60.Mice in each group were housed until P64 when pattern visual evoked potential (P-VEP) recordings were performed in both eyes.The amplitude and peak time of P100 wave were measured, and the contralateral/ipsilateral ratio (C/I) was calculated to evaluate the shift of ocular dominance.Twenty-four mice were randomly divided into MD group and MD+ myo-inositol group using the random number table method, with 12 mice in each group.RNA was extracted from the visual cortex of the two groups of mice, and transcriptomic sequencing and bioinformatics analysis were performed to screen differentially expressed genes.Six mice were randomly divided into MD group and MD+ myo-inositol group using the random number table method, with 3 mice in each group, and the expression changes of differentially expressed genes cell communication network factor 1( CCN1), fatty acid binding protein 7( Fabp7) and galectin-3 binding protein ( Lgals3bp) were verified by real-time fluorescence quantitative PCR.This study adhered to the Regulations on the Administration of Laboratory Animals (2017 Edition), and the research protocol was approved by the Animal Ethics Committee of Tianjin Medical University (No.TMUaMEC2022004). Results:The P-VEP results showed that the right eye P100 amplitudes in the normal control, MD, myo-inositol and MD+ myo-inositol groups were (89.04±19.87), (83.04±9.42), (88.14±21.75) and (61.75±15.42)μV, and the P100 wave peak time were (102.40±5.64), (101.50±8.26), (101.33±8.66) and (111.30±7.17)ms, and C/I were 2.38±0.17, 2.35±0.22, 2.41±0.31, and 1.65±0.24, respectively, with statistically significant overall differences ( F=5.844, 2.221, 16.634; all P<0.05).Compared with the normal control group, MD group and myo-inositol group, the MD+ myo-inositol group had a significant decrease in the P100 wave amplitude in the right eye, a significant prolongation of the P100 wave peak time, and a significant decrease in the C/I, with statistically significant differences (all P<0.05).There was no significant difference in P100 wave amplitude or peak time in the left eyes among the normal control, MD, myo-inositol and MD+ myo-inositol groups ( F=0.249, 1.356; both P>0.05).The transcriptome sequencing results showed that there were significant differences in the expression of 93 genes between the MD+ myo-inositol group and the MD group, among which the differential expression of CCN1, Fabp7 and Lgals3bp genes related to visual plasticity was particularly significant.The real-time fluorescence quantitative PCR results verified that the expression of CCN1 in the MD+ myo-inositol group was significantly decreased, and the expression of Fabp7 and Lgals3bp was significantly increased, with statistically significant differences ( t=17.561, 9.237, 12.710; all P<0.001). Conclusions:Myo-inositol can effectively reactivate ocular dominance plasticity in the visual cortex in adult mice, and may mediate this process by regulating the expression of specific genes CCN1, Fabp7, and Lgals3bp.

Objective:To investigate the effect of myo-inositol on the reactivation of ocular dominance plasticity in the visual cortex of adult mice and its mechanisms.Methods:Thirty-two male SPF-grade C57BL/6J mice at postnatal day 60 (P60) were randomly divided into four groups using a random number table: normal control group, monocular form deprivation (MD) group, myo-inositol group (myo-inositol administered to normal mice), and MD+ myo-inositol group (myo-inositol administered to MD mice), with 8 mice in each group.The right eyes of MD group and MD+ myo-inositol group received MD on P60.Mice in each group were housed until P64 when pattern visual evoked potential (P-VEP) recordings were performed in both eyes.The amplitude and peak time of P100 wave were measured, and the contralateral/ipsilateral ratio (C/I) was calculated to evaluate the shift of ocular dominance.Twenty-four mice were randomly divided into MD group and MD+ myo-inositol group using the random number table method, with 12 mice in each group.RNA was extracted from the visual cortex of the two groups of mice, and transcriptomic sequencing and bioinformatics analysis were performed to screen differentially expressed genes.Six mice were randomly divided into MD group and MD+ myo-inositol group using the random number table method, with 3 mice in each group, and the expression changes of differentially expressed genes cell communication network factor 1( CCN1), fatty acid binding protein 7( Fabp7) and galectin-3 binding protein ( Lgals3bp) were verified by real-time fluorescence quantitative PCR.This study adhered to the Regulations on the Administration of Laboratory Animals (2017 Edition), and the research protocol was approved by the Animal Ethics Committee of Tianjin Medical University (No.TMUaMEC2022004). Results:The P-VEP results showed that the right eye P100 amplitudes in the normal control, MD, myo-inositol and MD+ myo-inositol groups were (89.04±19.87), (83.04±9.42), (88.14±21.75) and (61.75±15.42)μV, and the P100 wave peak time were (102.40±5.64), (101.50±8.26), (101.33±8.66) and (111.30±7.17)ms, and C/I were 2.38±0.17, 2.35±0.22, 2.41±0.31, and 1.65±0.24, respectively, with statistically significant overall differences ( F=5.844, 2.221, 16.634; all P<0.05).Compared with the normal control group, MD group and myo-inositol group, the MD+ myo-inositol group had a significant decrease in the P100 wave amplitude in the right eye, a significant prolongation of the P100 wave peak time, and a significant decrease in the C/I, with statistically significant differences (all P<0.05).There was no significant difference in P100 wave amplitude or peak time in the left eyes among the normal control, MD, myo-inositol and MD+ myo-inositol groups ( F=0.249, 1.356; both P>0.05).The transcriptome sequencing results showed that there were significant differences in the expression of 93 genes between the MD+ myo-inositol group and the MD group, among which the differential expression of CCN1, Fabp7 and Lgals3bp genes related to visual plasticity was particularly significant.The real-time fluorescence quantitative PCR results verified that the expression of CCN1 in the MD+ myo-inositol group was significantly decreased, and the expression of Fabp7 and Lgals3bp was significantly increased, with statistically significant differences ( t=17.561, 9.237, 12.710; all P<0.001). Conclusions:Myo-inositol can effectively reactivate ocular dominance plasticity in the visual cortex in adult mice, and may mediate this process by regulating the expression of specific genes CCN1, Fabp7, and Lgals3bp.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Objective To identify signals of adverse events associated with vaccines in electronic medical record data. Methods Data cleaning was performed on electronic medical records and vaccination data in Gansu Province from 2020 to 2022. Signal identification was performed using Apriori algorithm and Empirical Bayes Gamma-Poisson Shrinker (GPS) with stratification by gender and age group. Results A total of 33 statistical signals were identified, with 7 signals identified by the Apriori method and 26 signals identified by the GPS method. No overlapping signals were found between the two methods at two different signal thresholds. Conclusion The vaccine safety signals identified by GPS and Apriori in electronic medical records are reliable and accurate, but further research is needed to determine the correlation between the vaccine safety signals recognized by GPS algorithms.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.