ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system X_c^-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Paridis Rhizoma possesses the functions of clearing heat and detoxifying， alleviating swelling and relieving pain， cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer， lung cancer， gastric cancer， and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation， migration， and invasion of tumor cells， regulating cell cycle， inducing apoptotic and non-apoptotic death pathways， and regulating metabolism and tumor microenvironment. Furthermore， total saponins in Paridis Rhizoma showed anti-inflammatory， antioxidant， antimicrobial， hemostatic， and uterus-contracting activities. At the same time， they may induce apoptosis of normal cells， inflammation and oxidative stress， and metabolic disorders. In recent years， the reports of liver injury， reproductive injury， gastrointestinal injury， hemolysis， and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate， while oral administration may have hepatoenteric circulation. Meanwhile， due to the low solubility and activation of P-glycoprotein （P-gp） molecular pump， the prototype absorption， intestinal permeability， and recovery rate of total saponins in Paridis Rhizoma are poor， which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect， pharmacokinetics， and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure （CNKI）， VIP， and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords， hoping to provide references for the research， development， and clinical application of such components.

Objective To evaluate the characteristics of dose distribution of neuronal networks in vitro on microelectrode arrays(MEAs)under 2.6 GHz radiofrequency(RF)exposure.Methods The MEAs were coupled with a real-time RF exposure setup,and electromagnetic simulation software was used to calculate the RF dose absorbed in cultured neuronal networks.A fiber-optic temperature probe was used for experimental validation and monitoring of the cell temperature during RF exposure.The MEAs were used to record the electrical activity of neurons.Results For an input power of 1 W,a specific absorption rate(SAR)level of(15.51±2.48)W/kg was calculated,and the variability of the SAR distribution was 16%.In our experimental system,the temperature elevation of neurons was up to 0.15℃for an SAR of 4 W/kg RF exposure.Conclusion The exposure device can provide high SAR efficiency and uniformity in the 2.6 GHz band,which is suitable for studying the real-time effects of RF fields on the electrical activity of neuronal networks in the 5G network band.

As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P＜0.05),and the number of falls was significantly increased(P＜0.001).The expression level of TH protein in brain tissue was significantly decreased(P＜0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P＜0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P＜0.05,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P＜0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P＜0.05,P＜0.001),the falling latency was significantly prolonged(P＜0.05,P＜0.01),the times of falls was significantly reduced(P＜0.001),the expression level of TH protein in brain tissue was significantly increased(P＜0.01,P＜0.001),and the level of serum TNF-α was significantly decreased(P＜0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P＜0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P＜0.01,P＜0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P＜0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

OBJECTIVE To calculate the cost of centralized dispensing of four categories of drugs （ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions） in pharmacy intravenous admixture service （PIVAS）， and provide reference for setting charging standards for relevant departments. METHODS The operating costs of PIVAS in 12 medical institutions from Shaanxi province were collected through questionnaire survey， including labor costs， medical and health material costs， fixed asset depreciation and repair costs， water and electricity costs， and management costs. The operation time allocation coefficient method and workload allocation coefficient method were comprehensively used to allocate the above costs， and the unit preparation costs of four categories of drugs were calculated. RESULTS The average annual total costs of dispensing ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions in Shaanxi province were （2 195 900.25±1 680 893.73） yuan， （746 341.59±725 839.39） yuan， （331 420.15±183 258.83） yuan， and （330 322.68±277 281.70） yuan， respectively， with labor costs accounting for the highest proportion， averaging 85.49%. The costs of dispensing a set of ordinary drugs， antibacterial drugs， and hazardous drugs were 5.89， 7.60， and 14.37 yuan， respectively； the cost of dispensing one bag of parenteral nutrition solution was 32.15 yuan （excluding the cost of disposable intravenous nutrition bags）. CONCLUSIONS The cost calculation method and data of different types of intravenous drugs obtained in this study can provide reference for relevant departments to formulate and adjust PIVAS fee standards.

OBJECTIVE To calculate the cost of centralized dispensing of four categories of drugs （ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions） in pharmacy intravenous admixture service （PIVAS）， and provide reference for setting charging standards for relevant departments. METHODS The operating costs of PIVAS in 12 medical institutions from Shaanxi province were collected through questionnaire survey， including labor costs， medical and health material costs， fixed asset depreciation and repair costs， water and electricity costs， and management costs. The operation time allocation coefficient method and workload allocation coefficient method were comprehensively used to allocate the above costs， and the unit preparation costs of four categories of drugs were calculated. RESULTS The average annual total costs of dispensing ordinary drugs， antibacterial drugs， hazardous drugs， and parenteral nutrition solutions in Shaanxi province were （2 195 900.25±1 680 893.73） yuan， （746 341.59±725 839.39） yuan， （331 420.15±183 258.83） yuan， and （330 322.68±277 281.70） yuan， respectively， with labor costs accounting for the highest proportion， averaging 85.49%. The costs of dispensing a set of ordinary drugs， antibacterial drugs， and hazardous drugs were 5.89， 7.60， and 14.37 yuan， respectively； the cost of dispensing one bag of parenteral nutrition solution was 32.15 yuan （excluding the cost of disposable intravenous nutrition bags）. CONCLUSIONS The cost calculation method and data of different types of intravenous drugs obtained in this study can provide reference for relevant departments to formulate and adjust PIVAS fee standards.