Diabetic cardiomyopathy （DCM） is a common chronic complication of diabetes， categorized as consumptive thirst in traditional Chinese medicine （TCM）， and it subsequently gives rise to chest impediment. DCM is characterized by a complex pathogenesis and exhibits long-term progression with poor prognosis in clinical practice. Astragali Radix， as a medicinal material with edible value， possesses diverse active components including saponins， polysaccharides， and flavonoids. It has the effects of tonifying Qi， elevating Yang， promoting fluid production， nourishing blood， expressing toxin， and expelling pus. Modern pharmacological studies have confirmed that Astragali Radix and its active components exert therapeutic effects in various aspects such as inhibition of inflammation， alleviation of stress injury， regulation of programmed cell death， modulation of glucose and lipid metabolism， inhibition of myocardial fibrosis， and regulation of gut microbiota and metabolites， treating DCM in a multi-component， multi-target， and multi-pathway manner. The compatibility of Astragali Radix exerts both synergistic and antagonistic effects. The compound preparations and extracts of Astragali Radix are widely used in clinical practice， and the development of novel nano and gel materials and extracellular vesicles helps to improve the oral bioavailability， providing more possibilities for the clinical application of Astragali Radix in DCM， though its potential for clinical translation requires ongoing exploration. This review summarizes the TCM theoretical basis of Astragali Radix in the treatment of DCM， and integrates modern pharmacological research results to delve into the effects and mechanisms of the herb combinations， compound preparations， extracts， and new composite materials of Astragali Radix in the treatment of DCM， aiming to provide a reference for in-depth research and new drug development of Astragali Radix for DCM.

Objective:To explore the protective effect of lentivirus-mediated miR-140-5p overexpression on lipopolysaccha-ride-induced liver injury in rats.Methods:A total of 40 rats were randomly divided into control group,model group,miR-NC group and miR-140-5p-mimic group,with 10 rats in each group.Rats in miR-NC group and miR-140-5p-mimic group received tail vein injection of lentivirus empty vector miR-NC and recombinant miR-140-5p respectively,while rats in control group and model group received tail vein injection of normal saline.Three days later,rats in model group,miR-NC group and miR-140-5p-mimic group received intraperi-toneal injection of 10 mg/kg lipopolysaccharide,while rats in control group received intraperitoneal injection of normal saline.All rats were killed 12 hours after injection,and the serum levels of ALT,AST,endotoxin,TNF-α,IL-6,IL-1β,SOD,MDA and CAT were detected.Pathological morphology and apoptosis of liver tissue were observed by HE and TUNEL staining.TargetScanHuman was used to predicted binding site of miR-140-5p and TLR4,and double luciferase reporter gene assay was used to analyse the targeted regula-tion relationship between miR-140-5p and TLR4.Level of miR-140-5p in liver tissue was detected by qRT-PCR,mRNA and protein expressions of TLR4,MyD88 and NF-κB in liver tissue were detected by qRT-PCR and Western blot,and expression of p-NF-κB was detected by Western blot.Results:In control group,the hepatic lobule was clearly visible,and there was no hepatocyte degeneration,necrosis and inflammatory cell infiltration.Obvious hepatocyte necrosis,vacuolar degeneration,hyperemia and infiltration of inflam-matory cells into hepatic sinusoids were observed in model group and miR-NC group.Hepatocyte hyperemia,necrosis,vacuolar degen-eration and inflammatory cell infiltration in miR-140-5p-mimic group were significantly less than those in model group and miR-NC group.miR-140-5p can directly target TLR4.Compared with control group,levels of ALT,AST,endotoxin,apoptotic cells,TNF-α,IL-6,IL-1β,MDA,TLR4,MyD88 mRNA and protein,NF-κB mRNA,p-NF-κB in model group,miR-NC group and miR-140-5p-mimic group were increased(P<0.05),while SOD and CAT were decreased(P<0.05).Compared with model group and miR-NC group,levels of ALT,AST,endotoxin,apoptotic cells,TNF-α,IL-6,IL-1β,MDA,TLR4,MyD88 mRNA and protein,NF-κB mRNA and p-NF-κB in miR-140-5p-mimic group were decreased(P<0.05),while levels of SOD and CAT were increased(P<0.05).Conclusion:Overexpression of miR-140-5p can reduce the level of inflammatory reaction and oxidative stress in rats with lipopolysac-charide-induced liver injury,protect hepatocytes and reduce liver pathological injury,and its mechanism may be related to TLR4/MyD88/NF-κB signal pathway.

The aim of this study was to investigate the risk factors for brucellar spondylitis.Electronic medical record data for patients with brucellosis at Yidu Central Hospital in Weifang City were retrospectively collected from January 2018 to April 2024,including general data,clinical characteristics,and laboratory examinations.The patients were divided into a spinal in-volvement group and a no spinal involvement group.The risk factors for brucellar spondylitis were determined through multi-factorial logistic regression model analysis.Of the 124 patients with brucellosis,59 had brucellar spondylitis,and 65 had bru-cellosis alone.There were more patients with age ≥55 years(x2=17.71),time from onset to diagnosis ≥30 days(x2=26.17),and low back pain(x2=52.71)in the spinal involvement group than in the group without spinal involvement,and the difference was statistically significant(all P＜0.001);there were more patients with headaches in the group without spinal in-volvement than in the group with spinal involvement,and the difference was statistically significant(x2=8.34,P＜0.05).and there were more patients in the spinal involvement group with neutrophil percent(NEU％)(t=2.94),platelet count(PLT)(t=122.00),blood sedimentation rate(ESR)(Z=-6.74),C-reactive protein(CRP)(Z=-5.74),and interleukin-6(IL-6)(Z=-2.08)were higher in the spine-involved group than in the group without spine-involvement,and the differences were all statistically significant(all P＜0.05);Lactate dehydrogenase was significantly lower in the spine-involved group(LDH)than the group without spinal involvement(t=-2.04,P＜0.042).A multifactorial logistic regression analysis indicated that a du-ration of out-of-hospital symptoms ≥30 days(OR=6.265,95％CI 1.181-33.241),symptoms of low back pain(OR=14.885,95％CI 3.144-70.472),elevated PLT(OR=1.013,95％CI 1.004-1.023),and elevated ESR(OR=1.053,95％CI 1.008-1.100)were risk factors for brucellar spondylitis(all P＜0.05).The optimal cut-off values for ROC analysis were PLT＞278.5 ×109/L(sensitivity 89.2％,specificity 59.3％)and ESR＞16.5 mm/h(sensitivity 69.2％,specificity of 86.4％);using both PLT and ESR for diagnosis yielded an AUROC of 0.891(95％CI 0.831-0.950),a sensitivity of 86.2％,and a specificity of 84.7％.When patients with brucellosis present with symptoms of low back pain,a time from onset to diagnosis of ≥30 days,and markedly elevated ESR and PLT,lumbar magnetic resonance examination is recommended to rule out brucellar spondylitis,to enable early diagnosis and timely treatment,improve patient prognosis,shorten illness duration,and improve patient quality of life.

Objective:To explore the protective effect of lentivirus-mediated miR-140-5p overexpression on lipopolysaccha-ride-induced liver injury in rats.Methods:A total of 40 rats were randomly divided into control group,model group,miR-NC group and miR-140-5p-mimic group,with 10 rats in each group.Rats in miR-NC group and miR-140-5p-mimic group received tail vein injection of lentivirus empty vector miR-NC and recombinant miR-140-5p respectively,while rats in control group and model group received tail vein injection of normal saline.Three days later,rats in model group,miR-NC group and miR-140-5p-mimic group received intraperi-toneal injection of 10 mg/kg lipopolysaccharide,while rats in control group received intraperitoneal injection of normal saline.All rats were killed 12 hours after injection,and the serum levels of ALT,AST,endotoxin,TNF-α,IL-6,IL-1β,SOD,MDA and CAT were detected.Pathological morphology and apoptosis of liver tissue were observed by HE and TUNEL staining.TargetScanHuman was used to predicted binding site of miR-140-5p and TLR4,and double luciferase reporter gene assay was used to analyse the targeted regula-tion relationship between miR-140-5p and TLR4.Level of miR-140-5p in liver tissue was detected by qRT-PCR,mRNA and protein expressions of TLR4,MyD88 and NF-κB in liver tissue were detected by qRT-PCR and Western blot,and expression of p-NF-κB was detected by Western blot.Results:In control group,the hepatic lobule was clearly visible,and there was no hepatocyte degeneration,necrosis and inflammatory cell infiltration.Obvious hepatocyte necrosis,vacuolar degeneration,hyperemia and infiltration of inflam-matory cells into hepatic sinusoids were observed in model group and miR-NC group.Hepatocyte hyperemia,necrosis,vacuolar degen-eration and inflammatory cell infiltration in miR-140-5p-mimic group were significantly less than those in model group and miR-NC group.miR-140-5p can directly target TLR4.Compared with control group,levels of ALT,AST,endotoxin,apoptotic cells,TNF-α,IL-6,IL-1β,MDA,TLR4,MyD88 mRNA and protein,NF-κB mRNA,p-NF-κB in model group,miR-NC group and miR-140-5p-mimic group were increased(P<0.05),while SOD and CAT were decreased(P<0.05).Compared with model group and miR-NC group,levels of ALT,AST,endotoxin,apoptotic cells,TNF-α,IL-6,IL-1β,MDA,TLR4,MyD88 mRNA and protein,NF-κB mRNA and p-NF-κB in miR-140-5p-mimic group were decreased(P<0.05),while levels of SOD and CAT were increased(P<0.05).Conclusion:Overexpression of miR-140-5p can reduce the level of inflammatory reaction and oxidative stress in rats with lipopolysac-charide-induced liver injury,protect hepatocytes and reduce liver pathological injury,and its mechanism may be related to TLR4/MyD88/NF-κB signal pathway.

Objective To explore the effects of different education and examination methods on the examination results during the screening/evaluation of patent foramen ovale by contrast-enhanced transcranial Doppler(cTCD).Methods Patients who underwent cTCD screening/evaluation for patent foramen ovale in our hospital from May 2023 to February 2024 were retrospectively selected as the research subjects.The patients were divided into the observation group and the control group according to different education and examination methods during the peri-examination period.Patients who received video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe were included into the observation group,and patients who received artificial education,Valsalva maneuver,and injection of contrast agent with 10 mL syringe were included into the control group.The positive detection rate of patent foramen ovale,right-to-left shunt microbubble grading during Valsalva/modified Valsalva maneuver,systolic blood flow velocity,pulsatility index(PI),resistive index(RI),examination duration,total physician-patient communication time,whether occlusion surgery was performed,and patient satisfaction were compared between the two groups.Results The positive detection rate of patent foramen ovale by cTCD(82.93%vs.95.92%),the detection rate of the maximum amout(grade Ⅲ)of microbubbles(39.02%vs.61.22%),the total physician-patient communication time during the peri-examination period[11.30(10.00,14.00)minutes vs.8.23(7.00,10.00)minutes],the rate of occlusion surgery(48.78%vs.73.47%),and the total patient satisfaction(80.49%vs.91.84%)showed statistically significant differences between the control group and the observation group(P<0.05).Additionally,the receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)for diagnosing patent foramen ovale were 0.718 in the control group and 0.855 in the observation group.Conclusion Peri-examination interventions such as video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe can improve the positive detection rate of patent foramen ovale,reduce ineffective physician-patient communication,and improve patient satisfaction.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective To investigate the relationship between serum ATP binding cassette subfamily A member 1(ABCA1)and fatty acid binding protein 4(FABP4)levels and insulin resistance(IR)and pregnan-cy outcome in patients with gestational diabetes mellitus(GDM).Methods A total of 121 patients with GDM admitted to the hospital from October 2019 to October 2023(GDM group)and 65 healthy pregnant women during the same period(control group)were selected,and the patients with GDM were divided into a poor group(50 cases)and a good group(71 cases)according to the pregnancy outcome.Serum ABCA1 and FABP4 levels were detected by enzyme-linked immunosorbent assay,and Pearson correlation coefficients were used to analyze the correlation between the two and the IR index(MOMA-IR)assessed by steady state model.With pregnancy outcome in GDM patients as the dependent variable,multivariate Logistic regression was used to determine its influencing factors,and receiver operating characteristic curve was used to evaluate the predictive efficacy of serum ABCA1 and FABP4 levels.Results Serum ABCA1 level in the GDM group was lower than those in the control group,and FABP4 level and HOMA-IR were higher than those in the control group(t=12.818,P＜0.001,t=17.219,P＜0.001,t=17.543,P＜0.001).In the GDM patients,HOMA-IR was nega-tively correlated with serum ABCA1 levels and positively correlated with serum FABP4 levels(r=-0.739,t=0.724,both P＜0.001).The independent risk factors for adverse pregnancy outcomes in GDM patients were HOMA-IR(OR=1.449,95％CI:1.161-1.810)and FABP4(OR=1.024,95％CI:1.011-1.037),and the independent protective factor was ABCA1(OR=0.302,95％CI:0.163-0.559).The area under the curve of serum ABCA1 combined with FABP4 level to predict pregnancy outcome in GDM patients was 0.877(95％CI:0.805-0.930),which was greater than that of serum ABCA1 and FABP4 levels alone,which were predic-ted by 0.786(95％CI:0.702-0.855),0.787(95％CI:0.703-0.856).Conclusion Reduced serum ABCA1 levels and elevated FABP4 levels are associated with IR and adverse pregnancy outcomes in patients with GDM,and the combination of the two has high predictive efficacy.