1.Tianxiang Pills Alleviates Myocardial Cell Pyroptosis in Rat Model of Myocardial Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress via ROS/Caspase-1/GSDMD Signaling Pathway
Fei ZENG ; Hao HUANG ; Yu CAO ; Yaoming XI ; Jing LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):143-150
ObjectiveTo investigate the mechanism by which Tianxiang pills (TXP) alleviates myocardial cell pyroptosis in the rat model of myocardial ischemia/reperfusion (I/R) injury through modulating the reactive oxygen species (ROS)/cysteinyl aspartate-specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsA total of 54 SPF-grade adult male Sprague-Dawley rats were randomized into six groups (n=9): sham (thoracotomy only without ligation), I/R (left anterior descending coronary artery ligation for 30 min followed by reperfusion), NAC (positive control, N-acetylcysteine, 150 mg·kg-1, by gavage), low-dose Tianxiang pills (TXP-L, 2.5 g·kg-1, by gavage)], medium-dose Tianxiang pills (TXP-M, 5 g·kg-1, by gavage), and high-dose Tianxiang pills (TXP-H, 10 g·kg-1, by gavage). The fluorescent probe method was employed to measure the ROS level. Biochemical assay kits were employed to determine the Caspase-1 activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity. Myocardial infarct size was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blot analysis was performed to evaluate the expression levels of proteins in the ROS/Caspase-1/GSDMD pathway, including GSDMD, cleaved Caspase-1/Caspase-1 ratio, the N-terminal domain of GSDMD (GSDMD-N), and the p22-phox subunit of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the concentration of interleukin-1β (IL-1β). Transmission electron microscopy (TEM) was employed to observe mitochondrial structure and to score the degree of mitochondrial swelling. ResultsCompared with the Sham group, the I/R group exhibited elevated the levels of ROS, Caspase-1 activity, GSDMD expression, IL-1β concentration, MDA content, infarct area, mitochondrial swelling score, cleaved Caspase-1/Caspase-1, GSDMD-N, and p22phox and decreased activities of SOD and GSH-Px (P<0.05). Compared with the I/R group, NAC and different doses of TXP significantly reduced the ROS level, Caspase-1 activity, GSDMD expression, IL-1β concentration, MDA content, infarct area, and mitochondrial swelling score. Moreover, they downregulated the expression of cleaved Caspase-1/Caspase-1, GSDMD-N, and p22phox and increased the activities of SOD and GSH-Px (P<0.05). Furthermore, TXP exerted effects on ROS, MDA, SOD, GSH-Px, Caspase-1 activity, GSDMD expression, IL-1β concentration, cleaved Caspase-1/Caspase-1, GSDMD-N, p22phox, infarct area, and mitochondrial swelling score in a dose-dependent manner (P<0.05). ConclusionTianxiang pills alleviates myocardial I/R injury by mitigating oxidative stress and cell pyroptosis through the inhibition of the ROS/Caspase-1/GSDMD signaling pathway.
2.Trend analysis of changes in blood donor populations in CSBT sentinel sites from 2021 to 2025
Xiaojie GUO ; Junhong YANG ; Wenqin ZHU ; Ruru HE ; Guoqiang FENG ; Ruiqing JU ; Fei TANG ; Zhujiang YE ; Mingliang YUAN ; Xin CHEN ; Zhenping LU ; Dongfu XIE ; Qing XU ; Xia HUANG ; Jia ZENG
Chinese Journal of Blood Transfusion 2026;39(8):1052-1060
Objective: To analyze the structural changes in whole blood and apheresis platelet donations in Chinese Society of Blood Transfusion (CSBT) sentinel units from 2021 to 2025, and to provide evidence for donor recruitment and blood service management. Methods: Aggregated data reported by sentinel sites were collected and stratified according to six indicators: age, sex, donation history, donation volume, donation site, and organization mode. Pearson χ
test, Cramer′V coefficient, Cochran-Armitage trend test and simple linear regression were adopted for analysis. Results: A total of 16 256 973 whole blood donations and 1 576 546 apheresis platelet donations were included. Among whole-blood donations, the proportion of donors aged 18-22 years decreased from 27.30% to 10.60%. The proportion of male donors increased from 58.81% to 63.13%; the proportion of people aged 30 and above increased from 58.40% to 75.30%; the proportion of fixed locations rose from 28.37% to 36.57%; the proportion of social groups increased from 21.69% to 39.69%. The 400-mL donations decreased from 62.12% to 53.46%, while individually initiated voluntary donations remained above 50%. Apheresis platelet donations were predominantly from males, individuals aged 30-39 years, and repeat donors; 2-treatment-unit apheresis platelet donations increased from 67.19% to 74.93%, and individually initiated donations accounted for 92.97%-96.02%. Statistically significant overall annual compositional differences were observed for all six indicators (all P<0.001), whereas linear trends for some sub-categories were not statistically significant. Conclusion: In the participating CSBT sentinel units, among whole blood donations, the proportions of donors aged 18-22 years, university-organized group donations, and donations at blood mobiles decreased, whereas the proportions of organizational group donations and donations at fixed venues increased. The apheresis platelet donation cohort is relatively mature and is evolving toward a high-efficiency donation model. Individual voluntary donation remains the primary organization mode for both donation types. Strategies such as youth donor recruitment, optimized layout of fixed donation sites, and retention of repeat donors should be strengthened to improve the resilience of blood supply.
3.Cost-utility analysis of influenza vaccination among primary and secondary school students in Anshun City
LI Jiao, XU Fei, ZENG Fei, ZHANG Dandan, YANG Li, LIU Lili, LI Jun, ZHENG Changning, LIU Ming
Chinese Journal of School Health 2026;47(7):1040-1044
Objective:
To evaluate the cost utility of different influenza vaccination strategies for primary and secondary school students in Anshun City, so as to provide healtheconomic evidence for influenza prevention and control in this population.
Methods:
Based on the demographic data of 380 700 students aged 5-14 in Anshun City in 2024, a decision tree model for different influenza vaccination strategies was constructed. The incremental cost utility ratio (ICUR) and net monetary benefit (NMB) were calculated, and sensitivity analysis was performed to assess the robustness of the model results.
Results:
For influenza vaccination among primary and secondary school students in Anshun City, compared with the selfpaid strategy (2% coverage), the free strategy (45% coverage) and the target strategy (70% coverage) both yielded an ICUR of -7 874.29 yuan per quality adjusted life year (QALY). When using 1 and 3 times the per capita Gross Domestic Product (GDP) as the willingness to pay thresholds, the per capita Net Monetary Benefit (NMB) was 1 000, 1 600 and 2 900, 4 500 RMB, respectively. The number of influenza infections or school absenteeism decreased by 25% and 40%, while saving a total cost of (46.779 5 and 73.976 8) million yuan, and increasing QALY by 5 940.79 and 9 394.73, respectively. Sensitivity analysis showed that within the reasonable fluctuation range of parameters, the ICUR remained consistently lower than the one and three times willingness to pay. Furthermore, 99% of the simulation results for both the free and target strategies fell below those thresholds, indicating high robustness of the model results.
Conclusion
Implementing free and target influenza vaccination strategies for primary and secondary school students in Anshun City offer distinct cost utility advantages, and the advantage enhances as the vaccination coverage rate increases.
4.Optimization of Processing Technology of Calcined Pyritum Based on QbD Concept and Its XRD Fingerprint Analysis
Xin CHEN ; Jingwei ZHOU ; Haiying GOU ; Lei ZHONG ; Tianxing HE ; Wenbo FEI ; Jialiang ZOU ; Yue YANG ; Dewen ZENG ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):197-205
ObjectiveBased on the concept of quality by design(QbD), the processing process of calcined Pyritum was optimized, and its X-ray diffraction(XRD) fingerprint was established. MethodsThe safety, effectiveness and quality controllability of calcined Pyritum were taken as the quality profile(QTPP), the color, hardness, metallic luster, phase composition, the contents of heavy metals and hazardous elements were taken as the critical quality attributes(CQAs), and the calcination temperature, calcination time, paving thickness and particle size were determined as the critical process parameters(CPPs). Differential thermal analysis, X-ray diffraction(XRD) and inductively coupled plasma mass spectrometry(ICP-MS) were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then, based on the criteria importance through intercriteria correlation(CRITIC)-entropy weight method, the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process, and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures, and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS2 to Fe7S8 during the process of temperature increase, the color gradually deepened from dark yellow, and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows:calcination temperature at 750 ℃, calcination time of 2.5 h, paving thickness of 3 cm, particle size of 0.8-1.2 cm, vinegar quenching 1 time[Pyritum-vinegar(10∶3)]. After calcination, the internal structure of Pyritum was honeycomb-shaped, which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96, and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing, the dissolution of the effective components in Pyritum increases, and the contents of heavy metals and harmful substances decrease, reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible, and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.
5.Optimization of Processing Technology of Calcined Pyritum Based on QbD Concept and Its XRD Fingerprint Analysis
Xin CHEN ; Jingwei ZHOU ; Haiying GOU ; Lei ZHONG ; Tianxing HE ; Wenbo FEI ; Jialiang ZOU ; Yue YANG ; Dewen ZENG ; Lin CHEN ; Hongping CHEN ; Shilin CHEN ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):197-205
ObjectiveBased on the concept of quality by design(QbD), the processing process of calcined Pyritum was optimized, and its X-ray diffraction(XRD) fingerprint was established. MethodsThe safety, effectiveness and quality controllability of calcined Pyritum were taken as the quality profile(QTPP), the color, hardness, metallic luster, phase composition, the contents of heavy metals and hazardous elements were taken as the critical quality attributes(CQAs), and the calcination temperature, calcination time, paving thickness and particle size were determined as the critical process parameters(CPPs). Differential thermal analysis, X-ray diffraction(XRD) and inductively coupled plasma mass spectrometry(ICP-MS) were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then, based on the criteria importance through intercriteria correlation(CRITIC)-entropy weight method, the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process, and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures, and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS2 to Fe7S8 during the process of temperature increase, the color gradually deepened from dark yellow, and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows:calcination temperature at 750 ℃, calcination time of 2.5 h, paving thickness of 3 cm, particle size of 0.8-1.2 cm, vinegar quenching 1 time[Pyritum-vinegar(10∶3)]. After calcination, the internal structure of Pyritum was honeycomb-shaped, which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96, and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing, the dissolution of the effective components in Pyritum increases, and the contents of heavy metals and harmful substances decrease, reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible, and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.
6.p300 promotes hepatic lipid accumulation in dyslipidemia by regulating SREBP-1c acetylation
Nyewneh Abdul-Rauf NUHU ; Xiaoli LI ; Lu FANG ; Yongqing CAI ; Fei CHEN ; Lie YUAN ; Xiong YANG ; Qingsong JIANG ; Yinbo LIU ; Chao LIU ; Peiling ZHONG ; Menghua ZENG
Journal of Army Medical University 2025;47(22):2735-2748
Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.
7.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
8.Epidemiological survey of knee osteoarthritis and analysis of related risk factors among military personnel in plateau regions
Pei-Jie LI ; Yong-Jie QIAO ; Ya-Fei CAO ; Jian-Kang ZENG ; Fei TAN ; Jia-Huan LI ; Rui-Ling XU ; Shuo YE ; Sheng-Hu ZHOU
Medical Journal of Chinese People's Liberation Army 2025;50(11):1374-1381
Objective To investigate the epidemiological characteristics of knee osteoarthritis(KOA)among military personnel in plateau regions and to explore its risk factors.Methods From July 2023 to July 2024,a multi-stage stratified cluster random sampling method was employed to survey the prevalence of KOA and related risk factors among military personnel in the northwest plateau regions of China,covering different altitudes(1500-4500 m)and geographical areas(Gansu,Qinghai,Tibet,and Xinjiang).All study subjects were divided into KOA and non-KOA groups based on the presence or absence of KOA.Variables including age,gender,body mass index(BMI),education level,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury were selected for univariate analyses between groups.Variables with P<0.05 in the univariate analyses were included in the binary multifactor logistic regression to identify risk factors for KOA.Results A total of 3000 questionnaires were distributed,and 2854 valid questionnaires were collected,with a response rate of 95.13%.The sample included 2584 males and 270 females,with 510 cases of KOA,resulting in a prevalence rate of 17.9%.Univariate analysis showed that there were statistically significant differences between KOA and non-KOA groups in terms of age,BMI,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury(P<0.05).However,no significant differences were found in gender and education level(P>0.05).Binary multivariate logistic regression analysis revealed that older age(OR=1.382,P=0.017),higher BMI(P<0.01),smoking(OR=1.929,P<0.01),higher military rank(OR=1.485,P=0.007),being a member of the Armed Police(P<0.01),longer service duration(P<0.01),higher regional altitude(OR=1.459,P<0.01),lower annual average temperature(OR=1.188,P=0.001),longer training duration(P<0.01),higher perceived training intensity(OR=2.450,P<0.01),and history of knee injury(OR=2.768,P=0.002)were independent risk factors for KOA.Conclusions Older age,overweight/obesity,smoking,higher military rank,being a member of the Armed Police,longer service duration,higher altitude,cold climate,longer training duration,higher training intensity,and history of knee injury are independent risk factors for KOA among military personnel in the northwest plateau regions of China.
9.Mechanism by which sanguis draconis flavones regulating ROS/TXNIP pathway-mediated pyroptosis to ameliorate cerebral ischemia-reperfusion injury in rats
Chao-Xia ZHU ; Zhi-Ying LI ; Xiao-Fei LÜ ; Qian ZHAO ; Bao-Cang CHENG ; Hui-Jie YANG ; Li-Ping ZHOU ; Li-Min ZENG
Acta Anatomica Sinica 2025;56(6):673-680
Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P<0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P<0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.
10.Research Advances on Probiotics-assisted Therapy for Metabolic Dysfunction-Associated Fatty Liver Disease
Jia XIONG ; Jia ZENG ; Xiaoxian ZHOU ; Xin XU ; Yanjiao WANG ; Zhishuang WU ; Jianzhong YIN ; Fei MI
Journal of Kunming Medical University 2025;46(7):163-174
Metabolic dysfunction-associated steatotic liver disease(MASLD)is a chronic liver condition intricately linked to metabolic abnormalities such as obesity,type 2 diabetes,dyslipidemia,and hypertension.The global prevalence of MASLD continues to rise,posing a significant public health challenge.The pathogenesis of MASLD is multifactorial,with the"multiple-hit"hypothesis suggesting that hepatic lipid accumulation,insulin resistance,oxidative stress,gut microbiota dysbiosis,and genetic factors collectively drive disease progression.Currently,clinical management primarily relies on lifestyle interventions;however,there is a lack of targeted pharmacological interventions,and there is an urgent need to investigate novel adjunctive therapeutic strategies.In recent years,probiotics have demonstrated potential value in MASLD treatment due to their capacity to modulate gut microbiota,enhance insulin sensitivity,and reduce liver inflammation.This review systematically examines the pathogenesis of MASLD and the limitations of existing therapeutic approaches,synthesizing the latest evidence of probiotics-assisted therapy for MASLD from the perspectives of animal studies and clinical trials.By analyzing the target mechanisms and molecular pathways of different strains(e.g.,Bifidobacterium,Lactobacillus),this review explores the translational potential of probiotics in MASLD treatment,aiming to provide a theoretical foundation and future research directions.


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