OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

Stent migration is one of the common complications following transcatheter valve implantation. This study aims to design a "drum-shaped" balloon-expandable aortic valve stent to address this issue and conduct a mechanical analysis. The implantation process of the stent was evaluated using a method that combines numerical simulation and in vitro experiments. Furthermore, the fatigue process of the stent under pulsatile cyclic loading was simulated, and its fatigue performance was assessed using a Goodman diagram. The process of the stent migrating toward the left ventricular side was simulated, and the force-displacement curve of the stent was extracted to evaluate its anti- migration performance. The results showed that all five stent models could be crimped into a 14F sheath and enabled uniform expansion of the native valve leaflets. The stress in each stent was below the ultimate stress, so no fatigue fracture occurred. As the cell height ratio decreased, the contact area fraction between the stent and the aortic root gradually decreased. However, the mean contact force and the maximum anti-migration force first decreased and then increased. Specifically, model S5 had the smallest contact area fraction but the largest mean contact force and maximum anti-migration force, reaching approximately 0.16 MPa and 10.73 N, respectively. The designed stent achieves a "drum-shaped" change after expansion and has good anti-migration performance.
Stents ; Prosthesis Design ; Heart Valve Prosthesis ; Humans ; Aortic Valve/surgery* ; Stress, Mechanical ; Transcatheter Aortic Valve Replacement/instrumentation*

Understanding the metabolism of endogenous and exogenous substances in the human body is essential for elucidating disease mechanisms and evaluating the safety and efficacy of drug candidates during the drug development process. Recent advancements in artificial intelligence (AI), particularly in machine learning (ML) and deep learning (DL) techniques, have introduced innovative approaches to metabolism research, enabling more accurate predictions and insights. This paper emphasizes computational and AI-driven methodologies, highlighting how ML enhances predictive modeling for human metabolism at the molecular level and facilitates integration into genome-scale metabolic models (GEMs) at the omics level. Challenges still remain, including data heterogeneity and model interpretability. This work aims to provide valuable insights and references for researchers in drug discovery and development, ultimately contributing to the advancement of precision medicine.

According to the theory of "toxin accumulation damaging yin"， the accumulation of pathological products and the disruption of homeostasis in the pre-metastatic niche （PMN） of malignant tumors correspond to "toxin accumulation" and "yin damage" respectively. During the dynamic evolution of PMN， the main pathogenesis in the initial stage is healthy qi deficiency and phlegm congestion， obstruction in the ying （营） and wei （卫） level， for which the therapeutic approach is fortifying spleen and warming yang， reinforcing healthy qi， consolidating the root， and assissting in resolving phlegm. In the progression stage， the predominant mechanism is mutual binding of phlegm and stasis， with collateral damage and pathological transformation. Treatment should focus on resolving phlegm and eliminating stasis， using insect-derived medicinals to attack accumulation and block pathological transmission. In the terminal stage， the main pathogenesis involves phlegm-stasis transforming into fire， with depletion of qi and yin， for which it is suggested to replenish qi and nourish yin， combine clearing and tonifying methods to control fire-toxin. After the PMN has formed， pathogenic toxin may flow along the collaterals， tending to lodge in corresponding viscera with functional imbalance and deviation between deficiency and excess， eventually giving rise to malignant tumors. Understanding the pathogenesis of the PMN in the malignant tumors based on the "toxin accumulation damaging yin" theory may provide a valuable perspective for developing traditional Chinese medicine strategies for the prevention and treatment of tumor metastasis.

Objective To analyze blood lipid levels in patients with myelodysplastic syndrome(MDS)and further explore the factors associated with abnormal blood lipids.Methods Eighty-eight newly diagnosed MDS patients were selected as the study group,and 100 healthy subjects were selected as the control group.Fasting blood lipid levels,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein A1(ApoA1)and ApoB were detected before treatment in the study group and the control group.The differences of serum lipid levels in MDS patients with different WHO-MDS classification,modified International Prognostic Score System(IPSS-R)karyotype,risk stratification and TP53 mutation were investigated.The correlation between ApoA1 level and clinical indicators of MDS patients was analyzed,and clinical indicators of different ApoA1 level groups were compared.Results The levels of TC,HDL-C,LDL-C,ApoA1 and ApoB were significantly lower in the study group than those in the control group(P＜0.01).There were no significant differences in TG,TC,HDL-C,LDL-C,ApoA1 and ApoB levels between different subgroups.The ApoA1 level was lower in the IPSS-R high-risk stratification group than that of the IPSS-R low-risk stratification group(P＜0.05).There were no significant differences in lipid levels between the different karyotype groups.The level of ApoA1 was lower in the TP53 mutant group than that in the non-TP53 mutant group(P＜0.05).Correlation analysis showed that ApoA1 level was positively correlated with body mass index(BMI,P＜0.05),and negatively correlated with patient age,percentage of bone marrow original cells,IPSS-R karyotype grouping,IPSS-R risk grouping and TP53 gene mutation(P＜0.05).The BMI level was lower in the low ApoA1 group than that of the high ApoA1 group(P＜0.05).The percentage of bone marrow original cells and TP53 gene mutation rate of MDS patients were higher in the low ApoA1 group than those in the high ApoA1 group(P＜0.05).Conclusion The plasma lipid level in MDS patients is significantly lower than that of healthy controls,and levels of ApoA1 varied significantly in different disease states,which may be associated with TP53 gene mutation.

AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.

Objective To investigate the effects of oral probiotics on gut microbiota diversity,colony structure,and intergroup differences in mice with subcutaneous colon cancer tumors,based on 16S rRNA sequencing technology.Methods Twenty-four 6-week-old male BALB/c mice were divided randomly into normal control group(NC group,n = 8),model group(M group,n = 8),and probiotic + model group(PM group,n = 8)after adaptive feeding for 1 week.Mice in the PM group were given 200 μL probiotic mixed solution(Bifidobacterium longum and Lactobacillus delbrueckii subsp.bulgaricus mixed lyophilized powder,2×108 colony-forming units)by gavage three times/week for 7 weeks,while the M group and PM group received 200 μL normal saline.At 10 weeks old,0.2 mL CT26.WT cell suspension(1×107/mL)was inoculated subcutaneously into the left hind limbs of M group and PM group,while NC group were inoculated with 0.2 mL normal saline.The general state of mice was observed,the growth of subcutaneous tumor was monitored,and the changes of intestinal flora structure were detected by 16S rRNA sequencing.Results The subcutaneous tumors of the M group were prominent,and the subcutaneous tumor volume and weight of the PM group were significantly reduced(P<0.05).Compared with NC group,Alpha diversity index was lower in the M group,and a significant difference of Beta diversity inter groups(P<0.01).And supplementation of probiotics had a certain effect on gut microbiota diversity in the M group.Compared with M group,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Bacteroides were higher in the PM group,while the relative abundance of Firmicutes,Desulfobacterota,Lachnospiraceae_NK4A136_group,Alistipes were lower in the PM group.LEfSe analysis showed that Muribaculaceae and Bacteroides in the PM group were different species with high abundance(LDA values>4).Conclusions Oral probiotics may improve the gut microbiota by increasing the relative abundance of beneficial Muribaculaceae and Bacteroides in subcutaneous tumors in mice with colon cancer.

Objective:To explore the effect of hallux nail flap design assisted with 3D printing in reconstruction of thumb defect in degloving injury.Methods:From January 2020 to March 2022, 16 patients with thumb defect caused by degloving injury with intact digit flexor and extensor tendons were treated. The patients were 11 males and 5 females, aged 20 to 52 years old, with an average age of 31 years old. The injured patient's hands were firstly scanned by CT and the 3D models were created to map the profile of the tissues required for reconstruction. Photopolymer templates for the defects in thumb were then 3D printed. The printed templates were put on the great toes and accordingly the hallux nail flaps were designed and harvested. The degloving wound of thumb was repaired by the hallux nail flap. Donor sites were repaired with artificial dermis in 6 patients and with ilioinguinal flaps in 10 patients. The effect of surgery was observed at outpatient clinic during postoperative follow-up. The survival of the hallux nail flap and the recovery of the donor site were observed. Function recovery were evaluated according to the Evaluation Standard of Finger Replantation and Reconstruction of Hand Surgery Society of Chinese Medical Association.Results:All the harvested hallux nail flaps matched with the profiles of recipient sites. All the hallux nail flaps survived over 4 to 30 months of follow-up, in an average of 16 months. Appearance of all hallux nail flaps was similar to normal thumbs, with good fingerprint and nails. Sensation recovery were S 3-S 4, with TPD at 4-7 mm. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 15 thumbs were excellent and 1 was good. Conclusion:Application of 3D printing assisted hallux nail flap transfer in reconstruction of defect of thumb in degloving injury can precisely design and harvest the required tissue and minimise a damage to the donor great toe. It improves the appearance of thumb as well as patient satisfaction. It is practical in reconstruction of the defect of thumb in degloving injury.

Objective:To evaluate the efficacy and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with HIV-1 or chronic HBV infection through observing the dynamic changes in antibody responses to two-dose inactivated SARS-CoV-2 vaccines.Methods:This cohort study recruited 169 people (including 39 with HIV-1 infection, 36 with chronic HBV infection and 94 individuals without chronic diseases) who completed two doses (prime and boost) of inactivated SARS-CoV-2 vaccination from January to December 2021. The levels of SARS-CoV-2 IgM and IgG antibodies at 14 d, one month and two months after boosting and neutralizing antibodies at one month were detected by chemiluminescence immunoassay and competitive ELISA method.Results:The positive rates of antibodies against SARS-CoV-2 in the HIV-1 and HBV groups were higher at one month after booster immunization, but significantly decreases at two months. The double-negative rate of SARS-CoV-2 IgM and IgG antibodies was higher in the HIV-1 and HBV groups than in the control group. The single positive rate of IgG antibody at one month in the control group was 2.01-fold higher than that of the HIV-1 group and 3.17-fold higher than that of the HBV group. The single positive rate of IgG antibody in people aged 18-39 years in each group was higher than that in the 40-59 age group. The antibody persistence was better in the HBV group than in the HIV-1 group, and the levels of IgG antibody in the HBV group was higher than that in the HIV-1 group. The neutralizing capacity of serum antibodies was significantly lower in the HIV-1 group than in the other groups ( P<0.000 1). The inhibition rate of serum neutralizing antibodies in the HBV group was lower than that in the control group among people aged 18-39 years [(34.050±6.031)% vs (64.220±3.845)%, t=4.43, P<0.000 1]. SARS-CoV-2-specific antibody responses were induced in 73.08% (19/26) of the patients aged 18-39 years in the HIV-1 group and 80.00% (4/5) in the HBV group. Conclusions:There were differences in the antibody responses to inactivated SARS-CoV-2 vaccines between different age groups, and infectious diseases affected the positive rates of antibodies and the neutralizing capability against SARS-CoV-2.