Objective To exPlore the effect of samPle_solVent comPositions on the determination of AstragaliⅣby high Performance liquid chromatograPh_ eVaPoratiVe light scattering detector ( HPLC_ELSD ) . Methods Radix astragali and ganduqing granules serVed as samPles. Methanol,90%methanol,80%methanol,70%methanol,32%acetonitrile,15%acetonitrile, and water were samPle solVents. HPLC_ELSD was used to determine content of astragalosideⅣ. Results The results showed that the 90%methanol solution was an aPProPriate samPle solVent with good system suitability,Precision,accuracy,and,linearity etc. . Conclusion This method benefits the quality control of astragalosideⅣin Radix astragali and agents containing Radix astragali.

Background The impact of cold spells on population health can be categorized into an independent main effect of extreme low temperatures and an added effect of prolonged low temperatures. However, studies on the added effects of cold spells on hospitalizations remain limited. Objective To investigate the added effects of cold spells on hospitalizations of residents in Hengyang City, Hunan Province, and to provide a scientific basis for establishing a cold spell early warning system. Methods Daily meteorological data, air pollutant data, and hospitalization data from six tertiary hospitals of four districts in Hengyang City from 2017 to 2023 were collected. A generalized linear model (GLM) combined with a distributed lag nonlinear model (DLNM) was used to assess the added effects of cold spells on non-accidental hospitalizations, as well as hospitalizations for circulatory system diseases and respiratory system diseases, after controlling the main effect of temperature. The modifying effects of cold spell characteristics (intensity and duration) and individual characteristics (gender and age) were also analyzed. Results Compared with non-cold spell periods, the relative risks (RRs) of total non-accidental hospitalizations and hospitalizations across disease categories, genders, and age groups were elevated during cold spells of varying intensities and durations. However, the total effects of cold spells exhibited a "U-shape" nonlinear relationship with intensity and decreased with prolonged duration. During high-intensity cold spells (daily average temperature < P₅ and lasting ≥ 2 d), the RR (95%CI) for non-accidental hospitalizations was 1.71 (1.21, 2.42); the RRs (95%CIs) for males and females were 1.99 (1.38, 2.84) and 1.47 (1.00, 2.16), respectively; for individuals < 65 years and ≥ 65 years, the RRs (95%CIs) were 1.59 (1.12, 2.26) and 1.93 (1.27, 2.92), respectively; and for circulatory and respiratory system diseases, the RRs (95%CIs) were 1.84 (1.22, 2.79) and 1.07 (0.71, 1.60), respectively. No statistically significant differences were observed between the above subgroups. The single-day lagged effects of cold spells displayed a two-peaked pattern. The single-day lag RR for total non-accidental hospitalizations peaked at lag 1 d after cold spell exposure, declined thereafter, and began to rise again after lag 5 d, reaching a second peak at lag 12–13 d before gradually decreasing. The lagged effects remained statistically significant during lag 8–18 d. The lag patterns of cold spell associations across disease categories, genders, and age groups were largely consistent with those of total hospitalizations. Conclusion Cold spells have a significant impact on non-accidental hospitalizations of residents in Hengyang City, with notable lagged effects. The findings provide important theoretical support for establishing a more targeted cold spell early warning system.

Depression is a kind of complex mental illness， which is mainly treated by western medicine at present， but the effect of western antidepressant drugs is not good due to the combined influence of side effects and individual differences of patients. Depression is a "stagnation syndrome" in traditional Chinese medicine， and its treatment principle is to disperse stagnated liver Qi for relieving Qi stagnation. The classic traditional Chinese medicine formula Chaihu Shugansan （CHSGS） has a long history of treating depression and demonstrates significant therapeutic efficacy. Clinically， the addition and subtraction of CHSGS is flexible， but the properties of the active ingredients are vague， and the mechanism and function are unclear. In order to elucidate the pharmacodynamic basis and antidepressant mechanism of CHSGS， this article reviews the pharmacodynamic material basis of CHSGS， clinical research and antidepressant mechanism research progress. Clinically， CHSGS can treat various types of depression such as primary depression， post-stroke depression， and postpartum depression. This article summarizes 32 main ingredients of CHSGS， among which albiflorin， ferulic acid， naringin， hesperidin， saikosaponin a， glycyrrhetinic acid， tangeretin， meranzin hydrate， nobiletin and glycyrrhizic acid are the quality markers （Q-markers） for the antidepressant effect of CHSGS. The antidepressant mechanism of CHSGS is complex， including regulating monoamine neurotransmitters， hypothalamic-pituitary-adrenal （HPA） axis， neurotrophic factors， inflammatory response， cell damage-related pathways， oxidative stress， etc. This article helps to deeply understand the pharmacodynamic basis and mechanism of CHSGS in treating depression， and provides a theoretical basis for the clinical application of CHSGS in treating depression and the development of antidepressant drugs.

Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

OBJECTIVE：To prelimi narily investigate the possible mechanism of orazamide to prevent anti-tuberculosis drug-induced liver injury （ATB-DILI）. METHODS ：A total of 60 Kunming mice were randomly divided into blank group ，model group，positive control group [diammonium glycyrrhizinate 60 mg/（kg·d）]，orazamide low-dose ，medium-dose and high-dose groups [ 80，160，320 mg/（kg·d）]，with 10 mice in each group. Except for blank group ，other groups were given isoniazid [ 75 mg/（kg·d）]+rifampicin [ 75 mg/（kg·d）] for 14 days intragastrically to induce ATB-DILI model. At the same time ，administration groups were given relevant medicine intragastrically ，blank group and model group were given normal saline intragastrically. The administration volume was 20 mL/（kg·d），once a day ，for consecutive 14 days. The general conditions of the mice were observed and recorded every day ，such as growth and development ，mental and diet state. After last medication ，liver index was calculated ， and HE staining was adopted to observe pathological changes of liver tissue of mice. The positive expression of high mobility group protein B 1 （HMGB1） and NF-κ B in liver tissue were detected by streptavidin biotin-peroxidase complex （SABC） immuno- histochemistry. The serum levels of liver function indexes in serum ，the protein expression of advanced glycation end product receptor（RAGE）and TNF-α in liver tissue were detected by ELISA. RESULTS：Compared with blank group ，the growth and development of mice in the model group were slow ，and their appetite and spirit were poor. The liver index ，serum levels of TBIL ， DBIL，ALT，AST，ALP，TBA and γ-GT were increased significantly （P＜0.05）. Structural disorder of liver lobules ，degeneration and necrosis of liver cells and inflammatory cell infiltration were observed. The expression of HMGB 1，NF-κB，RAGE and TNF-α in liver tissue were elevated significantly （P＜0.05）. Compared with model group ，the general condition of mice were all improved to different extents in orazamide low-dose ，medium-dose and high-dose groups ，positive control group ，while liver index and above serum indexes were all decreased significantly （P＜0.05）. The pathological changes of liver tissue were all improved to different extents ，while the protein expression of HMGB 1，NF-κB，RAGE and TNF-α were all decreased significantly（P＜0.05）. The improvement of above indexes in orazamide high-dose group were all significantly better than orazamide low-dose and medium-dose groups （P＜0.05）；the levels of ALP and TBA in orazamide high-dose group were significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Orazamide can prevent ATB-DILI induced by isoniazid combined with rifampicin in mice，the mechanism of which may be associated with down-regulating the protein expression of HMGB 1 and RAGE in liver tissue and inhibiting the secretion of inflammatory factors.

In recent years， the field of network pharmacology （NP） has developed rapidly， but the flawed and routine workflow has seriously affected the scientificity and reliability of NP analysis results. For complex diseases caused by environmental and genetic factors， symptomatic treatment or drugs targeting a single pathophysiological process cannot prevent or delay the progression of the disease， so the drug development fails or withdraws from the market. Therefore， there is an urgent need to develop new ideas for NP analysis that combines multiple pathophysiological processes. The key pathophysiological process is an important and complete set of pathological changes in the process of the occurrence， development， and outcome of the disease， which represents the current comprehensive and profound understanding of the nature of the disease. In order to improve the quality of NP research and promote the healthy development of the NP field， this paper proposes a new idea of NP analysis based on key pathophysiological processes. Based on the long-term clinical practice of traditional Chinese medicine and the key pathophysiological process of the disease， the method comprehensively analyzes the pharmacological mechanism and active ingredients of traditional Chinese medicine compound from the perspective of key pathophysiological process， which increases the scientifically， reliability， and repeatability of the analysis results. This paper takes Alzheimer's disease （AD） as an example to illustrate the necessity， feasibility， main workflow， advantages， and disadvantages of this method， and it is expected to screen disease-modifying drugs that prevent or reverse the course of the disease and promote the clinical transformation of research results.

Network pharmacology （NP） is a novel interdisciplinary subject based on the combination of systems biology， multi-omics theory， computer synthesize， network database， and so on. It is widely used in traditional Chinese medicine （TCM） for active component screening， compatibility rule， pharmacological mechanism， and toxicity-efficacy network. Domestic NP-related papers began to boost from 2017， but some research showed abnormal "homogenization" in the screening of key components. Due to the non-standard and unreasonable situation in early NP analysis， the screening results always contained the same and widely-existed 200-500 Chinese medicine substances as the key components for TCM compounds， regardless of the various “disease-treatment-medicine” approaches to the study. If the "homogenization" phenomenon cannot be promptly clarified and corrected， it will lead to the misunderstanding that the components such quercetin， kaempferol， and sitosterol are "guaranteed to cure all diseases"， which overestimates the pharmacological weights of the components in each disease. This phenomenon seriously interferes the selection and quality control of Q-Markers related to TCM compounds. It violates and negates the scientific connotation of "treating the same disease with different therapies" and "treating different diseases with the same therapy" guided by the holistic view and the theory of syndrome differentiation and treatment. In the long term， the "homogenization" phenomenon may even hinder the healthy development of NP in TCM. Based on TCM theory and modern medicine， this paper started with the "thomogenization" of component screening in NP， and analyzed from the three module of "tphenomenon consequences"， "tcause exploration"， and "tsolving strategies"， thus providing important references for NP research methods.

Acetyl-CoA Carboxylase ; metabolism ; Cell Line ; Curcumin ; pharmacology ; Hepatocytes ; drug effects ; metabolism ; Humans

OBJECTIVE: To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms. METHODS: We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor). RESULTS: In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis. CONCLUSIONS ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.
Acetates ; pharmacology ; Apoptosis ; drug effects ; genetics ; Autophagy ; drug effects ; Autophagy-Related Proteins ; metabolism ; Benzopyrans ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation ; Humans ; MCF-7 Cells ; Morpholines ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; metabolism ; Pyrans ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Triazines ; pharmacology ; Ubiquitin-Conjugating Enzymes ; metabolism

OBJECTIVE: To observe the effects and mechanism of uranium dust on collagen synthesis in fibroblastic cells.METHODS: i) RAW264. 7 macrophages were divided into solvent-control group and dust-affected group,and then treated with 0 and 120 mg / L( final concentration) uranium dust suspension for 0,2,4,8,16,24 and 32 hours. The supernatants of cells from these two groups were collected,and transforming growth factor beta 1( TGF-β1) levels were measured by enzyme-linked immunosorbent assay( ELISA). The best time phase was defined,and the supernatant of RAW264. 7 macrophages culture were separated as the conditioned medium( CM) for subsequent experiments. ii) Normal mouse lung fibroblasts L929 cells were divided into control group and uranium dust group,and treated with the CM of solvent-control group and dust-affected group respectively. After cultivated for 0,6,12,18,24,30 and 36 hours,the expression of α-smooth muscle actin( α-SMA) in L929 cells was detected by immunocytochemistry. The levels of extrac ellular collagen type Ⅰ( Col Ⅰ),collagen type Ⅲ( Col Ⅲ) and hydroxyproline( HYP) were detected by ELISA.RESULTS: i) The level of TGF-β1 in RAW264. 7 macrophages supernatant of the dust-affected group was higher than that of the solvent-control group after treatment with uranium dust for 4 hours,and showed an increasing trend with increasing time during 4-24 hours( P < 0. 05). The peak value was in 24 hours. The best time phase was 24 hours and used for CM of the two groups in subsequent experiments. ii) Compared with the control group at the same time points, the α-SMA expressions of L929 cells in uranium dust group increased after treatment with CM for 18-36 hours( P < 0. 05),the levels of Col Ⅰ,Col Ⅲ and HYP in uranium dust group increased after treatment with CM for 12-36 hours( P < 0. 05); both the expression of α-SMA and levels of Col Ⅲ and HYP increased with increasing time,showing a time-effect relationship( P <0. 05). CONCLUSION: Uranium dust can induce macrophages to secret TGF-β1 and affect fibroblast,increase α-SMAexpression,and increase the Col Ⅰ,Col Ⅲ and HYP synthesis. These might be the important mechanisms of lung fibrosis.