OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Objective To explore the levels of plasma complement factor H(CFH)in peritoneal dialysis(PD)patients and its judging value for prognosis.Methods Eighty-two PD patients followed up by the Department of Nephrology,The Second Affiliated Hospital of Naval Medical University were included in the study.Patients were divided by the CFH levels based on immunoassay turbidimetric detection into low H factor group(＜320 μg/mL,n=41)and high H factor group(＞320 μg/mL,n=41),while 82 healthy individuals matched by gender and age were selected as the healthy control group.The correlation between plasma CFH and laboratory results,complications,and prognosis in PD patients was analyzed over a 3-year follow-up.Results There were no differences between the two groups in terms of gender,age,dialysis duration,urine output,and dialysis adequacy,whereas the plasma albumin,total protein and cholesterol were significantly lower in the low CFH group compared with the patients in the high CFH group(P＜0.05).During the 3-year follow-up,the incidence of peritonitis was significantly higher in the low CFH group than in the high CFH group(P＜0.05).Multivariate regression analysis further confirmed that low CFH level was an independent risk factor for the development of PD associated peritonitis(OR=4.24,95%CI 1.18-15.33).Conclusions Reduced levels of plasma CFH in PD patients might suggest the increased risk of hypoalbuminemia and PD-associated peritonitis.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

Objective To explore the clinical effect of umbilical moxibustion on chronic heart failure with yang deficiency and blood stasis and water retention syndrome.Methods 80 patients with chronic heart failure who were hospitalized in the Department of Cardiology,Shenzhen Hospital(Longgang),Beijing University of Chinese Medicine from January 1,2021 to December 31,2022 were selected as research samples and randomly divided into control group(40 cases,40 cases completed)and observation group(40 cases,40 cases completed).The control group received standard drug treatment,while the observation group received umbilical moxibustion treatment on the basis of drug treatment.Ten days after treatment,NT-proBNP,NYHA cardiac function classification,cardiac color Doppler indexes(including LVEF,LVEDD,LVSD),Minnesota quality of life score,6-minute walking distance and TCM syndrome score were compared between the two groups before and after treatment,and the occurrence of adverse reactions was monitored and recorded.Results The total effective rate in the observation group was higher than that in the control group(χ2=3.865,P=0.049).NYHA cardiac function classification,NT-proBNP,LVEF,LVEDD,LVESD and 6-minute walking distance in both groups were significantly improved compared with those before treatment,and the improvement of the above indexes in the observation group was more significant(P<0.05).The Minnesota quality of life score and TCM syndrome score of the two groups decreased compared with those before treatment,and the decline of the patients in the observation group exceeded that of the control group(P<0.05).During the treatment,the two groups had adverse reactions(such as gastrointestinal reaction,hypotension,skin allergy,etc.),and there was no difference between the two groups(P>0.05).Conclusion On the basis of drug therapy,umbilical moxibustion is better than simple drug therapy in treating chronic heart failure with yang deficiency,blood stasis and water stagnation,which can improve the cardiac function and quality of life of patients with chronic heart failure.

Chronic kidney disease-associated pruritus (CKD-aP), one of the most common and intolerable complications in hemodialysis patients, not only seriously affects patients' quality of life and physical and mental health, but also increases the risk of long-term mortality. The pathogenesis of CKD-aP remains unclear, and immune-inflammatory dysregulation, imbalance of endogenous opioid system, abnormal accumulation of metabolites, xerosis, abnormal histamine level as well as hyperparathyroidism, have all been shown to be associated with pruritus. There is a lack of satisfactory and effective treatment strategies for CKD-aP, which mainly include pharmacological treatment, non-pharmacological treatment and dialysis modality modification. This article mainly reviews recent advances in the pathogenesis and pharmacological treatment of pruritus among hemodialysis patients.

Objective To examine the current state of care services for geriatric osteoporotic fractures in Chinese hospitals and to provide a basis for the improvement of these services and the formulation of related policies.Methods In September to November 2023,a stratified convenience sampling method was used to investigate the implementation of care services for elderly patients with osteoporotic fractures in 621 hospitals across 31 provinces(autonomous regions and municipalities)in China.A self-designed questionnaire was utilized for this purpose.Results A total of 621 hospitals participated in the survey,with 432(69.57%)tertiary hospitals and 189(30.43%)secondary hospitals.Over 95%of hospitals provided health education on diet,medication,fall prevention,and early functional exercise for elderly fracture patients.Less than 80%of hospitals provide specialized training on osteoporosis treatment and secondary fracture prevention for medical staff.Only 263 hospitals(42.35%)routinely conduct bone density tests for patients over 50 years old with fractures,while 221 hospitals(35.59%)routinely conduct bone metabolic biochemical tests for such patients.Less than 50%of hospitals provide specialized services,such as geriatric osteoporotic fracture clinics,for elderly patients with osteoporotic fractures.Additionally,39.77%of hospital departments have not developed postoperative care plans for elderly patients with osteoporotic fractures.The lack of specialized care teams(91.63%),insufficient investment in care resources(88.08%),and the absence of policy support(77.45%)are identified as the primary factors impeding the provision of care services for elderly patients with osteoporotic fractures in hospitals.Although some care services in tertiary hospitals are superior to those in secondary hospitals(P<0.05),they are still far from adequate.Conclusion The development of care services for elderly patients with osteoporotic fractures in Chinese hospitals needs improvement.It is recommended to further standardize and enhance the content and methods of health education,intensify clinical assessments related to osteoporosis in elderly fracture patients,improve the professional care capabilities of medical staff,and at the same time,the state should introduce relevant policies to support and promote the construction and development of hospital care services for elderly osteoporotic fracture patients.

Objective:To analyze functional changes in macrophages in mouse models of vulvovaginal candidiasis (VVC) by modulating indoleamine 2,3-dioxygenase 1 (IDO1) .Methods:Forty specific-pathogen-free female ICR mice were randomly divided into 4 groups using a complete randomization method: a blank group, a VVC model group, a VVC model + 1-methyltryptophan (1-MT) group (referred to as the 1-MT group), a VVC model + interferon-γ (IFN-γ) group (referred to as the IFN-γ group), with 10 mice in each group. Except for the blank group, all the mice were injected subcutaneously with estradiol benzoate oil solution in the abdomen every other day for 6 days prior to modeling to induce pseudoestrus; after successful induction of pseudoestrus, the mice were inoculated vaginally with Candida albicans suspensions at a concentration of 2 × 10 9 CFU/ml once a day for 5 days to establish VVC mouse models, and subcutaneous injections of estradiol benzoate oil solution were continued simultaneously to maintain the pseudoestrus state; 1 day before inoculation with fungal suspensions, mice in the 1-MT group and IFN-γ group were pretreated with 1-MT and IFN-γ respectively, followed by once-daily same intervention for 6 consecutive days; mice in the blank group and VVC model group were intraperitoneally injected with physiological saline solution once a day for 6 consecutive days. On the 5th day of modeling, vaginal conditions in mice were observed and vaginal symptoms were scored; the vaginal lavage fluid was collected for smear microscopy and fungal colony counting; then, the mice were sacrificed, the vaginal tissues were collected and subjected to hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining, and the expression of IDO1 and the macrophage surface marker F4/80 was determined in the vaginal tissues by an immunofluorescence method; real-time fluorescence-based quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1) in the vaginal tissues, and Western blot analysis to determine the IDO1 protein expression in the vaginal tissues. One-way analysis of variance was used to analyze the differences in indices among groups, and Tukey test was used for multiple comparisons. Results:Smear microscopic examination of the vaginal lavage fluid on the 5th day of modeling showed elongated hyphae with a few spores in the VVC model group, a large number of elongated hyphae aggregating in clusters with surrounding spores in the 1-MT group, and a few thin and short hyphae with a large number of spores in the IFN-γ group. Compared with the VVC model group (360.0 ± 15.9), the fungal colony counts in the vaginal lavage fluid significantly increased in the 1-MT group (523.7 ± 67.7, P = 0.002), but significantly decreased in the IFN-γ group (258.3 ± 27.57, P = 0.026). HE staining and PAS staining showed small abscess formation in the epidermis and predominant infiltration of neutrophils throughout the epidermal and dermal layers with a large number of spores and a few hyphae in the VVC model group; thickened epidermis and diffuse inflammatory infiltration predominated by neutrophils in the dermis were seen in the 1-MT group, with a large number of hyphae and spores aggregating into clusters, which were predominated by hyphae; in the IFN-γ group, spores aggregated in the epidermis without obvious hyphae, and a small amount of inflammatory cells predominated by neutrophils infiltrated the dermis. Immunofluorescence assay revealed that the relative fluorescence intensities of IDO1 and F4/80 were highest in the IFN-γ group and the 1-MT group, respectively. Western blot analysis revealed that the IDO1 protein expression in the VVC model group was significantly higher than that in the blank group ( P < 0.001) and the 1-MT group ( P < 0.05), but significantly lower than that in the IFN-γ group ( P < 0.05). qPCR showed that iNOS mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.01), and increased in the IFN-γ group compared with the blank group, VVC model group and 1-MT group (all P < 0.001); Arg-1 mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.001) and IFN-γ group ( P < 0.01), and increased in the 1-MT group compared with the blank group, VVC model group, and IFN-γ group (all P < 0.001) . Conclusion:In the VVC mouse models, upregulation of IDO1 may cause macrophage polarization toward the M1 phenotype, and inhibition of IDO1 may cause increased macrophage recruitment and exacerbate the inflammatory response.