Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

BACKGROUND: The objective of this study was to investigate the potential link between myopia in adolescents and exposure to per- and polyfluoroalkyl substances (PFASs). METHODS: This investigation included 1971 subjects with accessible PFAS level data, myopia status, and associated variables from four cycles of the National Health and Nutritional Examination Survey (NHANES). The investigation focused on specific PFAS compounds found in the serum, including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), chosen for their frequent detection. Owing to the skewed nature of the PFAS level data, the PFAS levels were log-transformed (Ln-PFAS) prior to analysis. Logistic regression, restricted cubic spline modeling, subgroup analysis, and sensitivity analysis were used to examine the associations between exposure to PFASs and the onset of myopia. RESULTS: PFOA levels were significantly associated with myopia risk (OR: 1.33; 95% CI: 1.05-1.69; P = 0.019). More specifically, with respect to the first quartile, the second quartile (OR_Q2: 1.69; 95% CI: 1.16-2.46; P = 0.007), third quartile (OR_Q3: 1.45; 95% CI: 1.03-2.03; P = 0.035), and highest quartile (OR_Q4: 1.58; 95% CI: 1.12-2.21; P = 0.010) of participants presented with increased myopia risk. Mediation analysis revealed that PFOA and myopia risk were partially mediated by serum albumin (ALB), with a mediation percentage of 22.48% (P = 0.008). A nonlinear inverted U-shaped relationship was identified between the level of PFOA and myopia risk (P for nonlinearity = 0.005). CONCLUSION Our findings suggest a potential link between exposure to PFOA and the likelihood of myopia development in young individuals and a mediating effect of serum ALB on this relationship. Notably, PFOA was identified as a key PFAS significantly contributing to the observed link between PFAS exposure and myopia risk. The potential threat of PFOA to myopia should be examined further.
Humans ; Fluorocarbons/adverse effects* ; Myopia/blood* ; Adolescent ; Male ; Female ; Prevalence ; Environmental Exposure/adverse effects* ; Nutrition Surveys ; Environmental Pollutants/adverse effects* ; United States/epidemiology* ; Alkanesulfonic Acids/blood* ; Caprylates/blood* ; Serum Albumin/metabolism* ; Child ; Sulfonic Acids

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

By combing the application and funding situation of general， young scholar and regional scholar programs from National Natural Science Foundation of China（NSFC） in field of integrated traditional Chinese and western medicine in 2023， this paper summarizes the distribution of supporting units， application and funding hotspots， and the problems of application and funding projects in this discipline， in order to provide a reference for applicants and supporting organizations to understand the hotspot dynamics and reporting requirements of the discipline. In 2023， the discipline of integrated traditional Chinese and western medicine received a total of 2 793 applications， and there were 1 254 applications for general programs， 1 278 applications for young scholar programs， and 261 applications for regional scholar programs. The amounts of project funding obtained by the three were 145， 164 and 35， respectively， and the funding rates were 11.56%， 12.83% and 13.41% in that order. From the situation of obtaining funding， the age distribution of the project leaders who obtained funding for the general， young scholar and regional scholar programs were mainly distributed in the age of 40-46， 30-34， 38-44 years， respectively. Within the supported programs， the Chinese medicine affiliations accounted for 55.52%. With respect to research subjects， the proportion of one single Chinese herbs， or monomers， or extracts accounted for 29.4%， but the proportion of Chinese herb pairs or prescriptions accounted for 47.1%. Research hotspots included ferroptosis， bile acid metabolism， macrophages， mitochondria， microglia， exosomes， intestinal flora， microecology and so on. The current research mainly focused on the common key problems of the advantageous diseases of Chinese and western integrative medicine， but still need to be improved in the basic theories of Chinese and western medicine and multidisciplinary cross-disciplinary research.

Objective:To analyze the expression levels and clinical significance of interferon (IFN)-α/β in the renal cortex and serum of children with lupus nephritis (LN).Methods:A total of 32 children with LN diagnosed in the pediatric nephrology department of the Second Xiangya Hospital of Central South University from December 2017 to September 2020 were selected as the study subjects (LN group). The normal kidney control group consisted of 3 normal kidney transplant volunteers who underwent biopsy of kidney tissue (normal kidney control group), while 14 healthy children who underwent physical examination were collected as the normal control group. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), LN patients were divided into mild activity group ( n=8), moderate activity group ( n=9), and severe activity group ( n=15). According to the International Society of Nephrology/Society of Nephrology (ISN/RPS) 2003 LN classification criteria, pathological classification was performed (3 cases in the mild pathological damage group, 8 cases in the moderate pathological damage group, and 11 cases in the severe pathological damage group); Immunohistochemistry was used to detect the expression and distribution of IFN-α/β in glomeruli and renal interstitium; Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of IFN-α/β in serum samples and analyze its correlation with the pathological classification and disease activity of LN patients. Results:The serum and renal cortex IFN-α/β levels in the LN group were higher than those in the normal control group and normal kidney control group, respectively (all P<0.05). The average level of serum IFN-α/β in the heavy activity group was higher than that in the light and moderate activity groups (all P<0.05). The serum and renal cortex IFN-α/β levels in the severe pathological damage group were significantly higher than those in the mild and moderate pathological damage groups (all P<0.05). Conclusions:IFN-α/β in the renal cortex is closely related to renal injury in LN; Serum IFN-α/β can assist in evaluating the disease activity level of LN to a certain extent.

Objective To investigate the effect and molecular mechanism of tRF-1:30-Gln-CTG-4(tRF-1:30)on the expression of inflammatory factors in high glucose(HG)-induced renal tubular epithelial cells(RTECs).Methods RTECs were divided into the control group,the HG group,the HG+tRF-1:30 mimic group,the HG+tRF-1:30 negative control(NC)group,the HG+si-IKZF2 group and the HG+si-NC group.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of tRF-1:30,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1)and IKAROS family zinc finger protein 2(IKZF2).Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of TNF-α,IL-6 and MCP-1.Protein expression of IKZF2 was detected by Western blot assay.Dual-luciferase reporter assay was used to detect the targeting relationship between tRF-1:30 and IKZF2.Results The expression levels of inflammatory factors were elevated in HG-induced RTECs,and the expression level of tRF-1:30 was decreased(P＜0.05).Overexpression of tRF-1:30 significantly decreased expression levels of inflammatory factors in HG-induced RTECs(P＜0.05),and the expression level of IKZF2 was significantly increased(P＜0.05).Further knockdown of IKZF2 can inhibit the release of inflammatory factors,and the expression level of IKZF2 was down-regulated after overexpression of tRF-1:30.Double luciferase reporting experiment further verified the possible targeting relationship between tRF-1:30 and IKZF2.Conclusion Overexpression of tRF-1:30 inhibits the expression of inflammatory factors in HG-induced RTECs by target binding and negatively regulating the expression of IKZF2.

Objective To investigate the molecular typing,virulence,and drug resistance features of bacterial strains in a simultane-ous outbreak of paratyphoid fever A and B,and then provide evidence for the prevention and treatment of the simultaneous transmission of different types of paratyphoid fever.Methods The clinical data of 31 patients confirmed as paratyphoid fever in the Hospital of Xin-jiang Production and Construction Corps from September 2018 to November 2018 were retrospectively analyzed.The isolated strains were performed serotyping and drug sensitivity tests.The molecular typing and the detection of virulence and drug resistance genes were carried out by multiplex PCR,pulsed-field gel electrophoresis(PFGE),and multilocus sequence typing(MLST).Results A total of 32 strains of Salmonella paratyphi were isolated from 31 patients,with 19 strains classified as type A and 13 as type B.The intermedi-ate rates of all strains against ciprofloxacin were 100%.The molecular typing and serotyping results of 11 representative strains were consistent.The PFGE fingerprints of Salmonella paratyphi A and B were also consistent.The MLST of Salmonella paratyphi A was ST85,and that of Salmonella paratyphi B was ST86.All strains carried virulence island SPI1-SPI5 representative genes such as invA,sitC,sseL,sifA,mgtC,siiE,and sopB,and regulatory gene phoP.Salmonella paratyphi A also carried cytolethal distending toxin(CDT)genes with trimeric structure such as cdtB,pltA,and pltB.The virulence plasmid genes such as pefA,prot6E,and spvB were all negative.Conclusion The simultaneous transmission of Salmonella paratyphi A and B has the characteristics of high pathogenicity and poor sensitivity to ciprofloxacin,which should be highly concerned by clinical and laboratory personnel.

Objective:To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors.Methods:A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined.Results:Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion ( P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas ( P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA ( P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions:MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.