There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ²=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ²=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ²=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ²=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m^2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ²=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.
Male ; Humans ; Child ; Female ; Retrospective Studies ; Alkaline Phosphatase ; Kidney Failure, Chronic/therapy* ; Renal Insufficiency, Chronic/therapy* ; Hypertension ; Risk Factors ; Hypertrophy, Left Ventricular/etiology* ; Anemia/etiology*

BACKGROUND: To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools. METHODS: Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed. RESULTS: A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field. CONCLUSIONS Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.
Bibliometrics ; China ; Humans ; Medicine, Chinese Traditional ; Osteosarcoma/therapy* ; Publications

Aim To examine the therapeutic effects of DHZCP on carbon tetrachloride(CCl4)-induced chemical hepatic fibrosis model in rats and the mechanism of acid-sensitive ion channels 1a(ASIC1a)and vascular endothelial growth factor(VEGF)-related mechanisms.Methods The rats were injected intraperitoneally with CCl4 vegetable oil mixture to establish hepatic fibrosis model,and randomly divided into six groups:control group,hepatic fibrosis model group,DHZCP low dose group,DHZCP medium dose group,DHZCP high dose group and colchicine(Col)positive control group.HE staining was used to observe the pathological changes of hepatic structures in each group,Masson staining to view the production of collagen fibers in each group,and immunohistochemistry,Western blot,q-PCR to investigate the expression level of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I proteins.Results In model group,serum ALT and AST levels were obviously up-regulated,liver tissue structure was severely damaged,and ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I gene and protein expression levels were significantly elevated.Compared with model group,each treatment group of DHZCP could markedly alleviate the pathological changes of liver fibrosis caused by CCl4,significantly reduce the serum ALT and AST levels,and dose-dependently down-regulate the gene and protein expression levels of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I,etc.Conclusions DHZCP ameliorates hepatic fibrosis in rats,and its mechanism of action may be associated with the regulation of ASIC1a/VEGF.

Purpose::Terminal performance of a bullet in human body is critical for the treatment of gunshot injury and optimization of bullet design. The effects of the impact velocity ( v0) and the impact attack angle ( δ0) of the bullet on its terminal performance was investigated, using a new evaluation method (called expansion method) based on the expansion of cracks and the permanent cavity wall in ballistic gelatin. Methods::Ballistic gelatin was used to simulate human body. The 7.62 mm × 39 mm rifle bullets with different v0 (600-760 m/s) and δ0 (0°-6°) were fired into the gelatin blocks. The gelatin block was cut into slices of about 20 mm thickness. The cracks and the permanent cavity on each slice were obtained manually. The damaged gelatin was determined using two methods: expanding the permanent cavity but ignoring the cracks, and expanding both the permanent cavity and the cracks. The relations between the damaged gelatin and v0 and δ0 were obtained using linear fitting method. Results::According to the distribution of the damaged gelatin along the penetration depth, the damaged gelatin block could be divided into two parts: the less damaged part and the severely damaged part. The length of the less damaged part depends mostly on δ0; while the average damaged area of this part depends on both δ0 as well as v0. The cracks contributed significantly to the total volume of damaged gelatin, particularly when the expansion was larger than 1.9 mm. The total damaged gelatin increases with v0, δ0 and the expansion extent. The average length of equivalent cracks grew with v0 and δ0 when considering the cracks, and decreased with v0 when ignoring the cracks. Conclusion::The expansion method is suitable to investigate the influence of different factors of bullets on their terminal performance. The characteristics of the damaged gelatin have a linear relationship with the initial attack angle ( δ0) and the initial velocity ( v0) of the bullet.

A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg·L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg·L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.
Acetylcholinesterase ; Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Ascomycota ; chemistry ; classification ; isolation & purification ; Cholinesterase Inhibitors ; isolation & purification ; metabolism ; Endophytes ; classification ; isolation & purification ; Huperzia ; microbiology ; Mice ; RAW 264.7 Cells

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574^*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
Acrosome ; Adult ; China ; Codon, Nonsense ; Female ; Humans ; Male ; Membrane Proteins/genetics* ; Point Mutation ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Sequence Deletion ; Sperm Head ; Sperm Injections, Intracytoplasmic ; Teratozoospermia/genetics* ; Exome Sequencing

This study aimed to investigate the association between surfactant protein B (SP-B) polymorphisms and bronchopulmonary dysplasia (BPD) in Chinese Han infants. We performed a casecontrol study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction (PCR) and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the genotype distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in the genotype distribution of C/T1580 or A/G9306 between the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group (0.12 to 0.05, P=0.003), whereas the frequency of C-inv-C-A haplotype was higher in control group (0.19 to 0.05, P=0.000). In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymorphisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in determining susceptibility to BPD.
Bronchopulmonary Dysplasia ; ethnology ; genetics ; China ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; ethnology ; genetics ; Haplotypes ; genetics ; Humans ; Infant, Newborn ; Introns ; genetics ; Male ; Polymorphism, Single Nucleotide ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics

OBJECTIVETo investigate the effect of toluene diisocyanate (TDI) on the production of reactive oxygen species (ROS) and the permeability of human bronchial epithelial (HBE) cells.

METHODSTDI-human serum albumin (TDI-HSA) conjugate was prepared using a modified Son's method. MTT assay was used to assess HBE cell viability after exposure to different concentrations of TDI-HSA. The level of intracellular ROS of HBE cells was detected by flow cytometry with an oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) uploading, and the permeability of cell monolayer was assessed by detecting the transepithelial electrical resistance (TEER).

RESULTSThe exposure to 120 µg/ml TDI-HSA did not obviously affect the cell viability. Compared with the control group, the intracellular fluorescent intensity increased significantly in the cells exposed to 20, 60, and 100 µg/ml TDI-HSA (P<0.05). The intracellular ROS production increased significantly after 100 µg/ml TDI-HSA treatment (P<0.05), but the increment in ROS production was significantly suppressed by pretreatment of the cells with N-acetylcysteine (NAC) (P<0.05), which also enhanced the TEER decreased by TDI-HSA treatment (P<0.05).

CONCLUSIONSTDI enhances the permeability of HBE cell monolayer partially through a ROS-mediated pathway, suggesting the importance of oxidative stress in TDI-induced pulmonary diseases.

Bronchi ; cytology ; Cell Line ; Cell Membrane Permeability ; drug effects ; Epithelial Cells ; cytology ; metabolism ; Humans ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Serum Albumin ; pharmacology ; Toluene 2,4-Diisocyanate ; pharmacology

Objective To explore the clinical treatment efficacy of punch drainage combined with ventricle puncture in patients with senile hypertensive hemorrhage. Methods One hundred and sixty-eight patients with senile hypertensive hemorrhage, admitted to our hospital from March 2002 to February 2009, were treated by punch drainage combined with ventricle puncture and hematoma dissolution with urokinase. Meanwhile, follow-up for 6-12 months was performed to every patient; the postoperative treatment effects and complications were evaluated by Glasgow Outcome Scale; the relations between the prognosis and both the amount of intracerebral hemorrhage and grades of consciousness situation were statistically analyzed. Results Good prognosis was noted in 91 patients,mild disability in 41, severe disability and vegetative state in 13, and death in 23; few postoperative complications were noted. The prognoses were significantly different in patients with different amounts of intracerebral hemorrhage; so are those in patients with different grades of consciousness situation (P＜0.05); the prognosis of patients under grade Ⅰ-Ⅱ consciousness situation was better than that of patients under grade Ⅲ-Ⅳ consciousness situation and the prognosis of patients with hemorrhage between 30-70 mL was obviously better than that of patients with hemorrhage above 70 mL. Conclusion The punch drainage combined with ventricle puncture and hematoma dissolution with urokinase is an effective treatment method for patients with senile hypertensive intracerebral hematoma.