This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

Objective:To explore the correlations between the cerebral infarction area and cytokines and immune status in patients with acute ischemic stroke,and to provide the theoretical basis for immunotherapy of the patients with different degrees of cerebral infarction.Methods:Sixty-seven patients with acute ischemic stroke within 72 h of the onset were randomly selected according to the inclusion and exclusion criteria,and were divided into large-area cerebral infarction group(n=34)and non-large-area cerebral infarction group(n=33)on the basis of the biggest infarction area in the sequences of magnetic resonance diffusion-weighted imaging(CDWI).Clinical baseline characteristics such as gender,age,and medical history were collected from the patients in two groups,the serum levels of interleukin(IL)-2,IL-6,IL-10,and IL-17A,tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)were measured using flow cytometry;the absolute values of lymphocytes(LYM#),lymphocyte percentages(LYM％),and neutrophil/lymphocy ratios(NLR)in peripheral blood of the patients caiculated,and the ratios of IFN-γ/IL-4,TNF-α/IL-4,and TNF-α/IL-10 rations were also calculated.The values of National Institutes of Health Stroke Scale(NIHSS)scores of the patients were evaluatd on the basis of the assessment of clinical neurological signs.The correlations of the cerebral infarction area and NIHSS score,cytokines and immune status groups of the patients in two were tested by rank correlation analysis.Results:Compared with non-large-area cerebral infarction group,the serum levels of IL-2,IL-6,IL-10,IL-17A,TNF-α,and IFN-γ as well as the NLR in the peripheral blood of the patients in large-area cerebral infarction group were significantly increased(P＜0.01),while the LYM#,LYM％and TNF-α/IL-4 were significantly decreased(P＜0.01).There was a positive correlation between cerebral infarction area and NIHSS score in the patients in large-area cerebral infarction group(rs=0.521,P＜0.05),and there was a significantly positive correlation between cerebral infarct area and NIHSS score in the patients in non-large-area cerebral infarction group(rs=0.721,P＜0.001).The NIHSS scores were positively correlated with serum IL-6(rs=0.306,P=0.005),IL-4(rs=0.252,P＜0.001),IL-2(rs=0.109,P=0.025),IL-17A(rs=0.405,P＜0.001),and IFN-γ(rs=0.146,P＜0.001)levels in two groups;no correlations were found between NIHSS scores and TNF-α(rs=0.039,P=0.726)and IL-10(rs=0.121,P=0.192)levels.NIHSS scores of the patients in two groups had negative correlatious with the serum level of LYM#(rs=-0.026,P=0.036)and LYM％(rs=-0.008,P=0.002),and had positive correlated with NLR(rs=0.315,P=0.009).Conclusion:The infarction area of the patients with actue cerebral infarction is correlated with the NIHSS score,the inflammatory response,the degree of adaptive immune injury,and the immune status.The have positive correlation with cytokines and immune markers and the overall size of the infarction area.Compared with the patients with non-large-acea cerebral infarction,the immunosuppression of the patients with large-area infarcted areas is more likely to occure.

Objective To explore the efficacy of goal management training(GMT)on core symptoms and mental status in college students with attention deficit hyperactivity disorder(ADHD)inattentive type.Methods Delphi method was used to construct a GMT program for college students with inattentive ADHD.Then,totally 68 college students with inattentive ADHD were recruited through advertisements published by hospitals and universities(Second Affiliated Hospital of Army Medical University,and 3 universities in Chongqing from March to June 2024.The subjects were randomly divided into an intervention group(n=34)and a control group(n=34).The intervention group received GMT for 2 h,once a week,for 7 weeks,and the control group did not receive training for the time being.The 2 groups were evaluated within 1 week before and in 7 weeks after intervention by using Adult ADHD Self-Report Scale(ASRS),Dysregulation of Emotions Rating Scale(DERS),Generalized Anxiety Disorde-7(GAD-7),Patient Health Questionnaire-9(PHQ-9),Self-Compassion Scale(SCS),and Satisfaction with Life Scale(SWLS).Results ① The expert authority coefficient(Cr)of 2 rounds of expert consultation was 0.83,with a questionnaire recovery rate of 100%and 95%,respectively,the Kendall's coordination coefficient was 0.081(P<0.01)and 0.226(P<0.01),and the coefficient of variation was<0.3,indicating the results of the expert consultation were reliable.The constructed GMT program includes 1 first-level indicator,7 second-level indicators,and 20 third-level indicators.② After 7 weeks of GMT intervention,the interaction between the 2 groups and time showed that the experimental group obtained significant improvements than the control group in terms of inattention symptoms(Wald Chi-square=28.35,P<0.001),dysregulation of emotions(Wald Chi-square=23.81,P<0.001),anxiety(Wald Chi-square=22.79,P<0.001),depression(Wald Chi-square=20.52,P<0.001),self-compassion(Wald Chi-square=9.36,P<0.01),and life satisfaction(Wald Chi-square=3.97,P<0.05).Conclusion GMT intervention can significantly improve the core symptoms of college students with inattentive ADHD,reduce anxiety and depression levels,enhance their emotion regulation and self-compassion abilities,and improve their life satisfaction.

OBJECTIVE To explore the pharmacodynamic related substances and mechanism of Weining San(WNS) against gastric ulcer(GU) according to fingerprint and network pharmacology. METHODS Twelve batches of WNS fingerprints were established by HPLC, and methodological investigation was carried out. Combined with reference substances, characteristic peaks were identified, pharmacodynamic related substances were screened, and network pharmacological analysis was carried out. Using TCMIP and Swiss Target Prediction database to retrieve component targets; Using OMIM, GeneCards and Drugbank databases to retrieve GU disease targets, taking the intersection targets of components and diseases, using String database to construct protein-protein interaction network diagram, and analyzing topological parameters; Using Cytoscape 3.8.2 software to construct "component-disease-target" network diagram; GO and KEGG enrichment analysis of intersection targets were carried out by Metascape website. Then the alcoholic GU mouse model was established by intragastric administration of absolute ethanol to verify the results of network pharmacology prediction. RESUITS　The precision, stability and repeatability of HPLC fingerprint method were good. By comparison and comprehensive analysis of control substances, notoginsenoside R1, ginsenoside Rg1, militarine, ginsenoside Rb1, schisandrin, schisandrol B, deoxyschizandrin and schisantherin A were identified as pharmacodynamic related substances in WNS, which may play their role by regulating core targets such as AKT1, IL-6, STAT3, TNF, IL1B and key signal pathways such as PI3K-Akt and JAK-STAT. The gastric ulcer index, ulcer inhibition rate and HE staining showed that WNS could improve gastric mucosal injury in GU mice. The results of ELISA, WST-1 and TBA showed that WNS could decrease the levels of TNF-α, IL-6, IL-1β and MDA, and increase the levels of SOD and PGE2, suggesting that the anti-GU effect of WNS was related to the inhibition of inflammatory reaction and oxidative stress mechanism, which further verified the prediction of network pharmacology. CONCLUSION This study combines fingerprint analysis, network pharmacology, and animal experimental validation to explore the pharmacodynamic related substances and mechanisms of WNS anti-GU efficacy, providing reference for quality control and clinical research of WNS.

Objective:To evaluate the effect of health science popularization in child caregivers by using social media of WeChat and Weibo in China in 2020.Methods:A questionnaire was designed based on the knowledge of children health from January to March 2020, and the public were invited to participate in the survey by visiting the official accounts of WeChat and Weibo of China CDC to analyze the awareness of health related knowledge and the change of daily behaviors in the child caregivers.Results:In the 1 325 child caregivers included in this survey, the awareness rate of chronic disease reexamine was lowest (74.94%), and the awareness rate of quality-oriented education was highest (99.55%). In the 7 questions in the questionnaire, the correct answer rate of the question about the reexamine of chronic disease was <75.00% (below the standard), the correct answer rate to other six questions were all ≥75.00% (above the standard). Logistic regression analysis showed that the education levels of senior high school or technical secondary school, junior college, bachelor's degree, master's degree or above, being worker, business/service personnel, teacher and company employee were the influencing factors for the awareness of the chronic disease related knowledge in child caregivers (all P<0.05). The daily behaviors of child caregivers after acquiring health knowledge were significantly improved (all P<0.001). Conclusions:In the season with high incidence of respiratory diseases, the use of new media platforms, such as WeChat and Weibo, to conduct health education had a good performance, resulting in higher rate of knowledge about healthy parenting and a significant improvement in daily behaviors in child caregivers. The results showed that the health education about the reexamine of chronic diseases in children should be focused on child caregivers with low education level, especially workers, business/service personnel.

Objectives:To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed.Results:Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed.Conclusions:When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.