Objective To investigate the immediate therapeutic efficacy of Kuanxiong Aerosol on improving the angina pectoris in the patients complicated with intermediate coronary stenosis(ICS),and to observe its effect on resting full-cycle ratio(RFR),corrected TIMI(thrombolysis in myocardial infarction)frame count(CTFC)in angiography,and coronary serum inflammatory factors.Methods Sixty angina pectoris patients with ICS admitted to the Cardiovascular Department of Dade Road Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2023 to March 2024 were randomly divided into the trial group and the control group,with 30 patients in each group.The trial group was given four consecutive sprays of Kuanxiong Aerosol by sublingual spray,and the control group had no intervention but just was given the monitoring for 10 minutes.Before and after the intervention,the changes of coronary RFR,CTFC,Visual Analogue Scale(VAS)score of chest pain,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6)and lipoprotein-associated phospholipase A2(Lp-PLA2)in the two groups were observed.Moreover,the incidence of adverse reactions during the intervention in the two groups of patients was compared.Results(1)After the intervention,the coronary RFR value of the trial group was increased significantly compared with that before intervention(P<0.01),while the coronary RFR value of the control group was not increased significantly compared with that before intervention(P>0.05);the comparison between the two groups showed that the effect on increasing the coronary RFR value in the trial group was superior to that in the control group(P<0.05).(2)After intervention,the CTFC value of the trial group was significantly decreased compared with that before intervention(P<0.01),while the CTFC value of the control group was not significantly decreased compared with that before intervention(P>0.05);the intergroup comparison showed that the trial group tended to have a better effect on the decrease of CTFC value than the control group,but the difference being not statistically significant(P>0.05).(3)After the intervention,the chest pain VAS score of the trial group was significantly reduced compared with that before intervention(P<0.01),while the pre-and post-treatment changes of the score in the control group was not significant(P>0.05);the intergroup comparison showed that the decrease of the chest pain VAS score in the trial group was superior to that in the control group(P<0.01).In particular for immediate therapeutic efficacy,Kuanxiong Aerosol achieved the effective rate of 96.67%(29/30)for relieving chest pain 10 minutes after sublingual spraying,which was significantly superior to that of the control group[10.00%(3/30)],and the comparison between the two groups showed that the difference was statistically significant(P<0.001).(4)After the intervention,the Lp-LPA2 value of the trial group was decreased compared with that before intervention(P<0.05),while the CRP and IL-6 values of the trial group as well as the CRP,IL-6,and Lp-LPA2 values of the control group were all not significantly decreased compared with those before intervention(P>0.05).The intergroup comparison showed that the trial group's effect on the decrease of Lp-LPA2 value was significantly superior to that of the control group(P<0.05).(5)Before and after the intervention,no obvious changes of the general vital signs in the two groups were shown,no drug-related adverse occurred,either.Conclusion Kuanxiong Aerosol can immediately improve the coronary physiological function indicators of angina pectoris patients with ICS,increase the coronary flow rate,and inhibit inflammatory response of the coronary artery to some degree,thus to alleviate the symptoms of angina pectoris in patients with ICS.

Objective To prepare a postbiotic using soybean fermentation product of Lactobacillus paracasei TK1501 and evaluate its inhibitory effect against Helicobacter pylori(Hp)infection in mice.Methods L.paracasei TK1501 was cultured for 32 h at 37℃in an anaerobic condition for solid substrate fermentation with a solid to water ratio of 1:1.5 in the substrate and an inoculation density of 5×107 CFU/mL.The postbiotic was isolated and purified using macroporous resin XAD-16N adsorption,cation exchange chromatography and HPLC,and its stability and antibacterial activity were assessed.The inhibitory effect of this postbiotic against Hp infection was evaluated in a mouse model with gastric mucosal Hp infection,which were treated with the postbiotic via gavage for 4 weeks at the dose of 0.02 or 0.1 mL.Serum levels of TNF-α and IL-1β of the mice were analyzed after the treatments,and gastric tissues of the mice were collected for HE staining.Results L.paracasei TK1501 postbiotic could be easily degraded by protease and had good thermal stability and tolerance to exposures to acid,base,and organic solvents.In the in vitro experiment,the postbiotic showed strong inhibitory effects in bacterial cultures of Staphylococcus aureus,Hp and other common pathogenic bacteria without obviously affecting the resident bacteria in the digestive tract.In the mouse models,treatment with the postbiotic at the dose of 0.1 mL significantly alleviated Hp infection and lowered the serum levels of TNF-α and IL-1β of the mice.Conclusion L.paracasei TK1501 postbiotic has strong inhibitory effects on Hp and Staphylococcus aureus but not on normal intestinal flora in mice.

Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P＜0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P＜0.05 or P＜0.01),while there was no significant difference in the above parameters in the X-NC group(all P＞0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01),and there was no significant difference in all parameters in the X-NC group(all P＞0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model cali-bration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the thera-peutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine"disease syndrome"and"macro micro"system modeling to facilitate translational research in CHM formulas.

Objective To prepare a postbiotic using soybean fermentation product of Lactobacillus paracasei TK1501 and evaluate its inhibitory effect against Helicobacter pylori(Hp)infection in mice.Methods L.paracasei TK1501 was cultured for 32 h at 37℃in an anaerobic condition for solid substrate fermentation with a solid to water ratio of 1:1.5 in the substrate and an inoculation density of 5×107 CFU/mL.The postbiotic was isolated and purified using macroporous resin XAD-16N adsorption,cation exchange chromatography and HPLC,and its stability and antibacterial activity were assessed.The inhibitory effect of this postbiotic against Hp infection was evaluated in a mouse model with gastric mucosal Hp infection,which were treated with the postbiotic via gavage for 4 weeks at the dose of 0.02 or 0.1 mL.Serum levels of TNF-α and IL-1β of the mice were analyzed after the treatments,and gastric tissues of the mice were collected for HE staining.Results L.paracasei TK1501 postbiotic could be easily degraded by protease and had good thermal stability and tolerance to exposures to acid,base,and organic solvents.In the in vitro experiment,the postbiotic showed strong inhibitory effects in bacterial cultures of Staphylococcus aureus,Hp and other common pathogenic bacteria without obviously affecting the resident bacteria in the digestive tract.In the mouse models,treatment with the postbiotic at the dose of 0.1 mL significantly alleviated Hp infection and lowered the serum levels of TNF-α and IL-1β of the mice.Conclusion L.paracasei TK1501 postbiotic has strong inhibitory effects on Hp and Staphylococcus aureus but not on normal intestinal flora in mice.

OBJECTIVE To systematically evaluate the efficacy and safety of eltrombopag combined with immunosuppressive therapy （IST） for severe aplastic anemia （SAA）， and to provide evidence-based basis for clinical treatment of SAA. METHODS Retrieved from PubMed， Embase， Cochrane Library， ClinicalTrials.gov， VIP， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about eltrombopag combined with IST （trial group） versus IST alone （control group） were collected from the inception to May 2023. After data extraction and quality evaluation （Cochrane manual 5.1.0） of included studies， meta-analysis， subgroup analysis， sensitivity analysis and publication bias analysis were performed by using RevMan 5.4 software. RESULTS A total of 12 studies were screened， including 1 344 patients. Compared with control group， objective remission rate （ORR） （RR＝1.34， 95%CI was 1.06-1.69， P＝0.01） and complete response rate （CRR） （RR＝1.88， 95%CI was 1.31-2.71， P＝ 0.000 6） at 3 months， ORR （RR＝1.33，95%CI was 1.23-1.43， P＜0.000 01） and CRR （RR＝1.88，95%CI was 1.57-2.25，P＜0.000 01） at 6 months were significantly increased in trial group. There was no statistically significant difference between the two groups in ORR （RR＝0.99， 95%CI was 0.82-1.18， P＝0.88） and CRR （RR＝1.02， 95%CI was 0.78-1.34， P＝0.87） at 12 months， two-year overall survival （OS） rate （HR＝0.61， 95%CI was 0.31-1.22， P＝0.17）， two-year event-free survival （EFS） rate （HR＝0.81， 95%CI was 0.61-1.07， P＝0.14）， clone evolution rate（RR＝1.01， 95%CI was 0.51-2.00， P＝ 0.98） or the incidence of adverse drug reactions such as liver/renal insufficiency， rash （P＞0.05）. Results of subgroup analysis showed that ORR and CRR of trial group at 6 months were higher than those of the control group in RCT and the cohort study subgroups （P＜0.05）. There was no statistically significant difference in the two-year OS rate， two-year EFS rate or clone evolution rate between trial group and control group in the two subgroups （P＞0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS The addition of eltrombopag in the IST regimen of SAA can improve the early hematological remission rate of patients， has no significant impact on short-term survival， and will not increase the occurrence of adverse drug reactions and clonal evolution.

Objective: To study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity, so as to provide scientific basis for formulating personalized intervention measures based on genetic background in children with obesity. Methods: From September 2018 to June 2019, a total of 393 children aged 8-10 years in Beijing were enrolled in a cluster randomized controlled trial. Eight schools were randomly allocated into intervention group and control group at a ratio of 1∶1. Saliva DNA samples were collected to detect rs 12145833 polymorphism of SDCCAG 8 gene. The intervention group received a comprehensive intervention, while the control group received usual practice. Intervention measures included diet improvement, sports, school amd family sport. The obesity related indicators were measured at baseline and after the end of intervention 1 academic year. Multiple linear regression and Logistic regression were used to analyze the interaction between genes and intervention on obesity indicators. Results: In the intervention group, children with TT genotype of rs 12145833 of the SDCCAG 8 gene had less increase in systolic( β=4.56, 95%CI=1.84-7.28, P <0.01) and diastolic blood pressure( β=2.59, 95%CI=0.45-4.73, P <0.05) than those with GT and GG genotypes. In the control group, the systolic blood pressure of children with TT genotype increased more than those with GT and GG genotype( β=-2.86, 95%CI=-5.63--0.83, P <0.05). There was an interaction between rs 12145833 polymorphism of SDCCAG 8 gene and intervention on systolic blood pressure, diastolic blood pressure and body fat percentage in children( P <0.05). Conclusion Children with TT genotype of rs 12145833 in the SDCCAG 8 gene are more sensitive to obesity intervention than those with GG and GT genotypes, especially in the improvement of systolic blood pressure, diastolic blood pressure and body fat percentage. Further trials to study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity among different ethnic populations are needed.

Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.

Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.

OBJECTIVE To investigate the efficacy and adverse reaction of CD 19-targeted chimeric antigen receptor T cells （CAR-T）in the treatment of relapsed/refractory diffuse large B -cell lymphoma （R/R DLBCL ），so as to provide an evidence -based basis for more reasonable and efficient application of CAR -T. METHODS Retrieved from PubMed ，Embase，Cochrane， ClinicalTrials.gov，CNKI，Wanfang，VIP database ，the literature about CD 19 targeted CAR -T in the treatment of R/R DLBCL that were published from the inception to April 2022 were screened . Taking objective remission rate （ORR），complete remission rate （CRR）and incidence of adverse reactions as outcome indicators ，subgroup analysis was performed according to the costimulatory factor of CAR -T and the different types of research . R 4.1.2 software was used for meta -analysis，sensitivity analysis and publication bias analysis . RESULTS A total of 11 pieces of literature were screened ，involving 1 466 patients. The ORR of CD -19 targeted CAR -T cells in the treatment of R/R DLBCL was 72.1%（95% CI：62.3%-81.9%），the CRR was 50.8%（95% CI：41.1%- 60.5%），the incidence of cytokine release syndrome （CRS）was 77.5%（95% CI：65.6%-89.4%），the incidence of neurotoxicity was 41.4%（95% CI：26.8%-56.1%）. Results of subgroup analysis showed that the incidence of ORR ，CRR，CRS and neurotoxicity in costimulatory factor CD 28 subgroup were higher than those in 4-1BB subgroup . The incidence of ORR ，CRR，CRS and neurotoxicity in the observational experimental subgroup were higher than those in the intervention experimental subgroup . CONCLUSIONS CD19 targeted CAR -T has high ORR and CRR for R/R DLBCL ，as well as higher incidence of adverse reactions. Co-stimulatory factor CD 28 has higher ORR ，CRR， CRS incidence and neurotoxicity incidence than 4-1BB.