ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide （LPS）-induced acute kidney injury （AKI） rats based on the Kelch-like epichlorohydrin-related protein-1 （Keap1）/nuclear factor erythroid-2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway. MethodsSixty male SD rats were randomly divided into normal group， model group， quercetin high-dose （100 mg·kg^-1） and low-dose （10 mg·kg^-1） groups， ferroptosis inhibitor Ferrostatin 1 （FER1） group （5 mg·kg^-1）， and quercetin high-dose + Nrf2 inhibitor group （ML385， 30 mg·kg^-1）. Except for the normal group， the AKI rat model was established in each group by intraperitoneal injection of LPS （10 mg·kg^-1）. Following successful modeling， each treatment group received the corresponding dose of drug intervention， while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of Fe²⁺， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） in renal tissue were detected. Hematoxylin-eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species （ROS） levels in renal tissue were detected by immunofluorescence （IF）. The protein and mRNA expression levels of Keap1， Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， transferrin receptor （TFR1）， and kidney injury molecule-1 （KIM-1） were assessed by immunohistochemistry （IHC） and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the normal group， the model group exhibited significantly elevated serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue， and significantly reduced SOD and GSH levels （P<0.01）. Pathological injury in renal tissue was severe， with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly elevated， while those of Nrf2， HO-1， and GPX4 were significantly decreased （P<0.01）. Compared with the model group， serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction， while SOD and GSH levels were significantly increased （P<0.05）. Pathological injury in renal tissue was markedly alleviated， mitochondrial damage improved， and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly decreased， while those of Nrf2， HO-1， and GPX4 were significantly increased， with the most notable improvement in the high-dose quercetin group （P<0.05）. In comparison to the high-dose quercetin group， the ML385 group significantly weakened the protective effect of quercetin on AKI rats （P<0.05）. ConclusionQuercetin effectively inhibits ferroptosis， improves renal tissue injury， and repairs renal function in AKI rats， and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.

OBJECTIVE To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice. METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopolysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3+T， CD4+T， and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+ were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing. RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF- κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO，NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8+T lymphocytes in the spleen were reduced significantly （P＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3+T and CD4+T lymphocytes， and the CD4+/CD8+ ratio in the spleen were significantly increased （P＜0.05）； the abundance of Firmicutes， Actinobacteria， Akkermansia， and Lactobacillus genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group. CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Objective To observe the relationship between the expression of human matricellular protein 3(MATN3)and the pathological features,drug resistance,and prognosis of gastric cancer based on immunohistochemical method.Methods A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included.MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry.The expression of MATN3 was compared across pathological features.Patients were divided into sensitive and resistant groups based on chemotherapy resistance,and MATN3 expression was compared between these groups.The relationship between MATN3 and recurrence-free survival(RFS)and overall survival(OS)of gastric cancer patients was analyzed using Kaplan-Meier survival curves.Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients.Human gastric cancer cells MGC803 were transfected with MATN3.The cells were divided into a high expression group(LV-MATN3 group)and its control group(LV-NC group)and a low expression group(sh-MATN3 group)and its control group(sh-NC group).Cell proliferation was assessed using the CCK8 assay,cell migration and invasion were assessed using the Transwell assay,and MATN3 mRNA expression levels were measured using RT-qPCR.A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3,and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR.Results Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues(64.00%,64/100)compared to adjacent non-cancerous tissues(31.00%,31/100)(P＜0.05).High MATN3 expression was associated with age≥60 years old,tumor location in the gastric body,tumor size≥5 cm,lymph node metastasis(N1-N3),histological differentiation(moderate to high),tumor invasion depth(T3-T4),TNM stage(Ⅲ-Ⅳ),distant organ metastasis,recurrence,and mortality(P＜0.05).Among patients with chemotherapy resistance,the high MATN3 expression rate was 79.49%(31/39)in the resistant group compared to 54.10%(33/61)in the sensitive group(P＜0.05).Follow-up duration ranged from 11 to 22 months,with a 97.00%follow-up rate and 3 cases lost to follow-up.Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression(RFS:log-rank=17.291,P＜0.001;OS:log-rank=21.719,P＜0.001).Multivariate Cox analysis identified high MATN3 expression(hazard ratio[HR]=2.291,95%confidence interval[CI]:1.268-5.392),tumor location in the gastric body(HR=2.057,95%CI:1.441-5.666),lymph node metastasis(N1-N3)(HR=2.011,95%CI:1.010-2.274),tumor invasion depth(T3-T4)(H=2.977,95%CI:1.032-7.853),TNM stage Ⅲ-Ⅳ(HR=2.008,95%CI:1.049-3.902),and distant organ metastasis(HR=2.505,95%CI:1.529-5.000)as independent risk factors affecting RFS and OS(P＜0.05).Cell and animal experiments demonstrated that compared to the LV-NC group,the LV-MATN3 group exhibited significantly higher cell proliferation,migration,and invasion(P＜0.05),as well as increased tumor volume and MATN3 mRNA expression in tumor tissues(P＜0.05).Conversely,the sh-MATN3 group showed significantly reduced cell proliferation,migration,and invasion,along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group(P＜0.05).Conclusion MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features,drug resistance and poor prognosis.MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells,including proliferation,migration,and invasion.

Objective: To explore the role and mechanism of long noncoding RNA(lncRNA) AC005062.1 in colorectal cancer(CRC) cell proliferation and apoptosis. Methods: The analysis of GSE84983 and GSE 104364 was used to indicate the expression level lncRNA AC005062.1 in CRC. The tumor tissues(tumor group) and adjacent tissues(control group) of patients undergoing CRC surgery in the hospital tumor surgery department were collected. Eight pairs of tissues were randomly selected, and qPCR was used to detect the expression of lncRNA AC005062.1 in CRC tissues and paired adjacent tissues in the two groups. After using siRNA to down-regulate the expression of lncRNA AC005062.1 in CRC cells, CCK-8 assay was used to detect cell proliferation in two groups, flow cytometry was used to detect cell cycle and apoptosis in two groups, wound scratch test was used to detect cell migration in two groups, and the lncRNA was determined. The database was used to compare the localization of lncRNA AC005062.1 and MACC1 genes on staining. The expression levels of MACC1 transcription and protein levels in the control group and tumor group were detected by qPCR and Western blot, respectively. The lncRNA AC005062.1 in CRC cells was down-regulated, and the expression levels of MACC1 transcription and protein levels in the two groups of cells were detected by qPCR and Western blot, respectively. Results: The database analysis of GSE84983 and GSE104364 and the detection results of the two groups indicated that the lncRNA AC005062.1 was highly expressed in CRC. After down-regulation of lncRNA AC005062.1, the results of CCK-8 experiments showed that the proliferation rate of HT29 cells in the down-regulation group decreased. Flow cytometry showed that the number of apoptosis of HT29 cells in the down-regulated group increased, the proportion of G1 phase increased, and the proportion of S phase and G2 phase decreased. Western blot experiments showed that the expressions of cleaved-caspase3 and Bax in the down-regulated HT29 cells increased, while the expression of Bcl-2 decreased. Wound scratch experiments showed that the migration rate of HT29 cells in the down-regulated group was lower than that in the control group. The analysis of UCSC to compare the location of lncRNA ac005062.1 and MACC1 on chromosomes showed that they were located very close together. MACC1 was highly expressed in CRC and down-regulated lncRNA AC005062.1 expression in HT29 cells could reduce the expression of MACC1. Conclusion lncRNA AC005062.1 can inhibit the proliferation, cycle and migration of HT29 cells, and promote its apoptosis by regulating the expression of MACC1 in CRC.

Objective:To explore the relationship between carotid atherosclerosis (CAS) and bone metabolism marker osteocalcin (OC) in patients with type 2 diabetes (T2DM).Methods:A total of 100 patients with T2DM admitted to Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University) from January 2018 to August 2018 were selected as study subjects, and the carotid intima-media thickness (IMT) was detected.The patients were divided into CAS group and normal carotid IMT group (NC group), with 50 cases in each group.The levels of OC, fasting plasma glucose(FPG), fasting insulin(FINS), glycosylated hemoglobin(HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein (LDL-C), insulin resistance index (HOMA-IR) were compared between the two groups.Results:The OC level of the CAS group[(11.86±4.46)ng/mL] was significantly lower than that of the NC group[(23.94±4.52)ng/mL] ( t=-9.640, P=0.001). The LDL-C level of the CAS group[(2.89±0.82)mmol/L] was significantly higher than that of the NC group[(2.55±1.16)mmol/L]( t=2.03, P=0.049). Pearson correlation analysis showed that IMT was positively correlated with age, LDL-C, HbA1c ( r=0.285, 0.190, 0.173; P=0.000, 0.020, 0.035), and negatively correlated with OC ( r=-0.603, P=0.000). Conclusion:CAS in patients with T2DM is closely related to OC, and the reduction of OC levels may be a risk factor for CAS in T2DM patients.

Objective:To observe the influence of valsartan combined with Bailing capsules on urinary albumin excretion rate in early stage of type 2 diabetic nephropathy ( DN) , and explore its protection in early DN. Methods:Sixty patients with early DN were randomly divided into two groups. On the basis of diet control and blood glucose regulation, the control group (n=30) was given valsartan 160 mg, qd, while the prevention group (n=30) was treated by valsartan (160 mg·d-1) combined with Bailing capsules (2. 0g, po, tid), and the treatment course was 12 weeks. The urinary albumin excretion rate ( UAER) , mean arterial blood pressure ( MAP) , serum creat-inine ( Scr) and hemoglobin A1c ( HbA1c) were measured and compared before and after the treatment in the two groups. Results:UAER in the two groups was significantly reduced after the treatment compared with that before the treatment (P<0. 01), and that in the prevention group was obviously lower than that in the control group (P<0. 01). MAP in the two groups was significantly decreased after the treatment as well (P<0. 01), while there was no significant difference between the two groups. Scr and Hb Alc in the two groups showed no significant changes before and after the treatment (P>0. 05). Conclusion:Valsartan combined with Bailing capsules shows certain effects in the treatment of early stage of type 2 diabetic nephropathy by decreasing the urinary albumin excretion.

Objective:To assess the ability of axillary reverse mapping (ARM) to identify and preserve the arm lymphatics drainage as well as determine its ability to reduce lymphedema. Methods:A total of 300 breast cancer patients who underwent axillary lymph node dissection (ALND) from June 2009 to May 2011 were enrolled in this study. Methylene blue dye (2 mL to 3 mL) was injected into the ipsilateral upper inner arm along the medial intramuscular groove to map the upper extremity lymphatic drainage system prior to ALND. The blue lymphatic and lymph nodes were identified and preserved during the operation. The change in the arm circumference was the selected method of measurement. The difference in the bilateral upper arm circumference was recorded after 2 months (difference≥2 cm is defined as lymphedema). Results:The ARM was performed successfully in 195 (65%) of 300 patients. The incidence of lymphedema was significantly lower in the successfully mapped patients than in the failing mapping patients, with statistically significant difference during follow-up at 6, 12, 18, and 24 months post operation. Conclusion:The ARM technique can identify and preserve the arm lymphatics drainage and prevent upper extremity lymphedema after breast cancer axillary lymphadenectomy.

Stage assessment is an important part of standardized resident training.After two years of practice and exploration,Liaoning had established the complete examination and evaluation system including the theory test and skill test and this system was future improved through analyzing two years' results and summing up the experiences making it more suitable for residency training in the future.

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gossypol ; analogs & derivatives ; pharmacology ; Humans ; Light ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Transplantation ; Photochemotherapy ; Reactive Oxygen Species ; metabolism ; Singlet Oxygen ; metabolism ; Tumor Burden ; drug effects