Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

Microbial detection and control of traditional Chinese medicine(TCM) decoction pieces are crucial for the quality control of TCM preparations. It is also a key area of research in the measurement technology and equipment development for TCM manufacturing. Guided by TCM manufacturing measurement methodologies, this study presented a design of a novel portable microbial detection device, using Atractylodis Macrocephalae Rhizoma decoction pieces as a demonstration. Immunomagnetic separation technology was employed for specific isolation and labeling of target microorganisms. Enzymatic signal amplification was utilized to convert weak biological signals into colorimetric signals, constructing an optical biosensor. A self-developed smartphone APP was further applied to analyze the colorimetric signals and quantify target concentrations. A portable and automated detection system based on Arduino microcontroller was developed to automatically perform target microbial separation/extraction, as well as mimetic enzyme labeling and catalytic reactions. The developed equipment specifically focuses on the rapid and quantitative microbial analysis of TCM active pharmaceutical ingredients, intermediates in TCM manufacturing, and final TCM products. Experimental results demonstrate that the equipment could detect Salmonella in samples within 2 h, with a detection limit as low as 5.1 × 10~3 CFU·mL~(-1). The equipment enables the rapid detection of microorganisms in TCM decoction pieces, providing a potential technical solution for on-site rapid screening of microbial contamination indicators in TCM. It has broad application prospects in measurement technology for TCM manufacturing and offers strong technical support for the modernization, industrialization, and intelligent development of TCM.
Drugs, Chinese Herbal/analysis* ; Atractylodes/microbiology* ; Rhizome/microbiology* ; Biosensing Techniques/methods* ; Medicine, Chinese Traditional ; Colorimetry/instrumentation* ; Quality Control

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.

Objective In this study,inbred BALB/c mice infected with the pneumonia virus of mice(PVM)were used to establish an animal model of viral pneumonia,and the changes in the pro-inflammatory alarmin molecule,high mobility group box 1 protein(HMGB1),during PVM infection were observed,as well as the in vivo intervention effects of the HMGB1 inhibitor,glycyrrhizic acid(GA),on PVM-induced lung injury.Methods Three-week-old female BALB/c mice were randomly divided into three groups,each consisting of 6 mice.One group,uninfected by PVM,served as the control group(Control).The other two groups were inoculated intranasally with PVM at a dose of 1×104 50％tissue culture infective dose(TCID50)/25 μL,and subsequently treated with GA saline solution(GA group)or plain saline solution(normal saline,NS group)via gavage for 15 consecutive days.During this period,changes in body weight and appearance were monitored in each group.At the end of the experiment,lung tissue samples were collected from all groups.The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry.The expression levels of HMGB1 and its Toll-like receptor 4(TLR-4),advanced glycosylation end-product-specific receptor(AGER),and inflammatory cytokines such as interleukin(IL)-1β,IL-2,and tumor necrosis factor-α(TNF-α)in lung tissues of mice were measured using real time fluorescence quantitative PCR.Results Compared with the Control group,the NS group showed a significant weight loss after 6 days(P＜0.05).Histopathological tests revealed pronounced inflammatory lesions in their lungs.Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm,and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1,IL-1β,and IL-2 were significantly upregulated(P＜0.05).In the GA group,there was no significant change in the clinical symptoms or body weight.However,compared with the NS group,the pathological damages of lung tissues in the GA group were significantly reduced,and the expression levels of HMGB1,IL-1 β,IL-2,and interferon-γ(IFN-γ)in lung tissues were also significantly decreased(P＜0.05),although the expression level of AGER was significantly increased(P＜0.05).Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice,and GA can effectively alleviate the damages.Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin⁺/CD31⁺ ratio, rather than the number of CD31⁺ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Humans ; Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; Mice, Nude ; Glycogen Synthase Kinase 3 beta/genetics* ; beta Catenin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Desmin/therapeutic use* ; Ki-67 Antigen ; Cell Line, Tumor ; Hypoxia ; RNA, Messenger/therapeutic use* ; Cell Proliferation

This study aimed to provide a scientific basis for the application of the mycorrhizal planting technology of Dendrobium officinale by investigating the effects of mycorrhizal planting on the fingerprints of D. officinale and the content of six chemical components. Seventeen samples of D. officinale under mycorrhizal and conventional planting were collected from four regions, such as Jinhua of Zhejiang. The HPLC fingerprints were established to evaluate the similarity of the samples. The content of six chemical components of the samples was determined by HPLC. There were 15 common peaks in the fingerprints, and five of them were identified by marker compounds, which were naringenin, 4,4'-dihydroxy-3,5-dimethoxybibenzyl, 3,4'-dihydroxy-5-methoxybibenzyl, 3',4-dihydroxy-3,5'-dimethoxybibenzyl(gigantol), and 3,4-dihydroxy-4',5-dimethoxybibenzyl(DDB-2). The similarities of the fingerprints of mycorrhizal and conventional planting samples and the control fingerprint were in the ranges of 0.733-0.936 and 0.834-0.942, respectively. The influences of mycorrhizal planting on fingerprints were related to planting regions, the germplasm of D. officianle, and the amount of fungal agent. The content of six chemical components in the samples varied greatly, and the content of DDB-2 was the highest, ranging from 69.83 to 488.47 μg·g~(-1). The mycorrhizal planting samples from Chongming of Shanghai and Taizhou of Jiangsu showed an increase in the content of 5-6 components, while samples from Zhangzhou of Fujian and Jinhua of Zhejiang showed an increase in the content of 1-2 components. The results showed that mycorrhizal planting technology did not change the chemical profile of small molecular chemical components of D. officinale, but affected the content of chemical components such as bibenzyls, which has a good application prospect.
Dendrobium/chemistry* ; Mycorrhizae ; China ; Chromatography, High Pressure Liquid