OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC₅₀ = 6.40 ± 0.34 μmol·L^-1) and Ⅱ-2 (IC₅₀ = 7.15 ± 0.51 μmol·L^-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Formaldehyde is a prevalent organic solvent in industrial and indoor environment,which can seriously harm human health,so it is of great significance to develop highly sensitive formaldehyde sensors with fast response,low detection limit and long life.In this study,the NiO-In2O3 composite structure was prepared using indium-based metal organic framework(In-MOF)as the precursor,and the formaldehyde gas sensor was constructed with In2O3 and NiO-In2O3 composite structure as the sensitive material.The results demonstrated that the In2O3 material had a microflower-like structure,while the NiO-In2O3 composite structure was composed of NiO nanoparticles attached to the surface of In2O3.The sensor exhibited excellent detection performance for formaldehyde in the environment of relative humidity of 33%and 75%,especially the response characteristic of the NiO-In2O3 composite structure sensor to formaldehyde was considerably better than that of the In2O3 sensor under the same test conditions,which was closely related to the catalytic effect of NiO and the heterogeneous structure formed between NiO and In2O3.The NiO-In2O3 composite structure sensor had a response value of 21.3 and 12.6 to 10 μL/L formaldehyde when the relative humidity was 33%and 75%at 200℃.The response/recovery time was 4/6 s and 7/10 s,and the limit of detection(LOD)was 1.2×10-7 μL/L and 4.1×10-5 μL/L respectively.Meanwhile,the sensor had excellent selectivity and long-term stability.This sensor showed a wide application prospect in the field of high-performance detection of low concentration of formaldehyde gas.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To develop a health belief model(HBM)based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity.Methods The adolescents'alcohol-related cognitive scale was developed based on HBM model.By using purposive sampling,three general high schools in Qingpu District,Shanghai were selected.One-third of the classes from grades 10 and 11 in each school were randomly selected,and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability(internal consistency reliability and combination reliability)and validity(structural validity,convergent validity,discriminative validity and criterion validity).Results A total of 970 questionnaires were collected,of which 948 were valid,with an effective rate of 97.7%.The adolescents'alcohol-related cognitive scale contained 22 items.Five common factors were extracted from exploratory factor analysis,including perceived susceptibility,perceived severity,perceived benefits,perceived obstacles,and self-efficacy.The cumulative variance contribution rate reached 83.89%.The results of confirmatory factor analysis confirmed the overall fit of the model.The average variance extracted value(AVE)of each dimension was greater than 0.5,and the convergent validity of the model was ideal.The AVE square root of each dimension of the scale was greater than its correlation coefficient,indicating good discrimination validity.Cronbach's α coefficient of the total volume table was 0.892,indicating good overall reliability.Conclusion The adolescents'alcohol-related cognitive scale developed in this study has good reliability and validity,which can be used to measure adolescents'alcohol-related perceptions.

Objective: To analyze the status of excess heart age and its risk factors among Chinese residents aged 35 to 64 years. Methods: The study subjects were Chinese residents aged 35 to 64 years who completed the heart age assessment by WeChat official account "Heart Strengthening Action" through the internet from January 2018 to April 2021. Information such as age, gender, body mass index (BMI), blood pressure, total cholesterol (TC), smoking history, and diabetes history was collected. The heart age and excess heart age were calculated according to the characteristics of individual cardiovascular risk factors and the heart aging was defined as excess heart age≥5 years and 10 years respectively. The heart age and standardization rate were calculated respectively based on the population standardization of the 7th census in 2021.CA trend test was used to analyze the changing trend of excess heart age rate and population attributable risk (PAR) was used to calculate the contribution of risk factors. Results: The mean age of 429 047 subjects was (49.25±8.66) years. The male accounted for 51.17% (219 558/429 047) and the excess heart age was 7.00 (0.00, 11.00) years. The excess heart age rate defined by excess heart age≥5 years and ≥10 years was 57.02% (the standardized rate was 56.83%) and 38.02% (the standardized rate was 37.88%) respectively. With the increase of the age and number of risk factors, the excess heart age rate of the two definitions showed an upward trend according to the result of the trend test analysis (P<0.001). The top two risk factors of the PAR for excess heart age were overweight or obese and smoking. Among them, the male was smoking and overweight or obese, while the female was overweight or obese and having hypercholesterolemia. Conclusion: The excess heart age rate is high in Chinese residents aged 35 to 64 years and the contribution of overweight or obese, smoking and having hypercholesterolemia ranks high.
Humans ; Male ; Female ; Overweight ; Hypercholesterolemia/epidemiology* ; Risk Factors ; Obesity/epidemiology* ; Body Mass Index ; China/epidemiology*

Wound healing is a slow and complex biological process, including inflammatory reaction, cell proliferation, cell differentiation, cell migration, angiogenesis, extracellular matrix deposition, tissue remodeling, and so on. Wnt signaling pathway can be divided into classical pathway and non-classical pathway. Wnt classical pathway, also known as Wnt/β-catenin signaling pathway, plays an important role in cell differentiation, cell migration, and maintenance of tissue homeostasis. Many inflammatory factors and growth factors are involved in the upstream regulation of this pathway. The activation of Wnt/β-catenin signaling pathway plays an important role in the occurrence, development, regeneration, repair and related treatment of skin wounds. This article review the relationship between Wnt/β-catenin signaling pathway and wound healing, meanwhile summarizes its effects on important processes of wound healing, such as inflammation, cell proliferation, angiogenesis, hair follicle regeneration, and skin fibrosis, as well as the role of inhibitors of Wnt signaling pathway in wound healing.
Humans ; Wnt Signaling Pathway ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Inflammation ; Wound Healing

The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.
Glycyrrhiza uralensis/chemistry* ; Plant Components, Aerial/chemistry*