AIM: To analyze the value of blue-on-yellow perimetry(B/Y)combined with macular ganglion cells inner plexiform layer(GCIPL)detection in the early diagnosis of open angle glaucoma.METHODS: A prospective case-control study was conducted to collect 100 patients(174 eyes)from May 2023 to May 2024 in Eye Hospital of Wenzhou Medical University as the case group, and 20 healthy volunteers(40 eyes)as the control group. The case group was divided into high intraocular pressure group, suspected glaucoma group, and early glaucoma group based on the examination results. All study subjects underwent comprehensive ophthalmic examination, white-on-white perimetry(W/W)and B/Y examination, and swept source optical coherence tomography(SS-OCT)was used to scan the optic disc and macula to obtain relevant parameters. The value of B/Y combined with macular GCIPL in the diagnosis of open angle glaucoma was analyzed.RESULTS: In the case group, 30 cases(52 eyes)were diagnosed with early primary open angle glaucoma, 46 cases(82 eyes)were suspected of open angle glaucoma, and 24 cases(40 eyes)were diagnosed with high intraocular pressure. The W/W mean defect(MD)and B/Y-MD values in the early glaucoma group were lower than those in the control group, high intraocular pressure group, and suspected glaucoma group. The W/W pattern standard deviation(PSD)and B/Y-PSD values were higher than those in the control group, high intraocular pressure group, and suspected glaucoma group(all P<0.05). The W/W-MD and B/Y-MD values in the suspected glaucoma group were lower than those in the control group and the high intraocular pressure group(all P<0.05). The B/Y-MD values in the high intraocular pressure group were lower than those in the control group(P<0.05). The parameters of GCIPL in the macular area of the early glaucoma group were lower than those of the control group, high intraocular pressure group, and suspected glaucoma group(all P<0.05). The minimum GCIPL in the macular area of the suspected glaucoma group, as well as the upper and lower temporal areas, were lower than those of the control group and the high intraocular pressure group(all P<0.05). The average, upper, lower, temporal, 5:00, 6:00, and 12:00 positions of the retinal nerve fiber layer(RNFL)parameters around the optic disc in the early glaucoma group were lower than those in the control group, high intraocular pressure group, and suspected glaucoma group(all P<0.05). The average and upper RNFL parameters in the suspected glaucoma group were lower than those in the control group and high intraocular pressure group. The rim area of the optic nerve head(ONH)parameters in the early glaucoma group was smaller than that in the control group, high intraocular pressure group, and suspected glaucoma group, while the horizontal and vertical cup-to-disc ratio was higher than those in the control group, high intraocular pressure group, and suspected glaucoma group; the rim area of the suspected glaucoma group was smaller than that of the control group and high intraocular pressure group, and the horizontal and vertical cup-to-disc ratio were higher than those of the control group and high intraocular pressure group(all P<0.05). Receiver operating characteristic(ROC)curve was drawn, and the results showed that visual field parameters, macular GCIPL parameters, and RNFL parameters had certain diagnosibility for early open angle glaucoma and suspected glaucoma. Decision curve was drawn, and the results showed that when the threshold was between 0 and 1.0, the net return rate of diagnosing early open angle glaucoma with the combination of B/Y and macular GCIPL parameters was higher than the individual diagnostic efficacy of each indicator.CONCLUSION: The combination of B/Y and macular GCIPL detection can be an important means for the early diagnosis of glaucoma.

AIM: To analyze the changes of retinal structure and function before and after panretinal photocoagulation(PRP)in patients with proliferative diabetic retinopathy(PDR).METHODS: Prospective study. Totally 98 cases(98 eyes)of PDR patients who underwent PRP in Eye Hospital of Wenzhou Medical University from January 2022 to May 2023 were included. Optical coherence tomography angiography(OCTA)was used to detect central retinal thickness(CRT), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), foveal avascular zone(FAZ), deep vascular complex(DVC)blood flow density, superficial vascular complex(SVC)blood flow density before and at 1 wk, 1 and 3 mo after PRP. During the follow-up, 1 eye underwent vitrectomy, 2 eyes were lost to follow-up, and finally 95 eyes completed 1 a follow-up, with a loss rate of 3%. According to the visual prognosis at 1 a after treatment, the patients were divided into two groups: 73 eyes in good prognosis group and 22 eyes in poor prognosis group(including 9 eyes of visual disability and 13 eyes of visual regression). The changes in retinal structure and function before and after PRP treatment were compared between the two groups of patients, and the receiver operating characteristic(ROC)curve and decision curve were used to analyze the predictive value of retinal structure and function for PDR treatment.RESULTS: There were statistical significant differences in PDR staging, CRT, CMT, SFCT, DVC blood flow density, and SVC blood flow density between the two groups of patients before treatment(all P<0.05). At 1 wk, 1 and 3 mo after treatment, the FAZ area of both groups decreased compared to before treatment, while the blood flow density of DVC and SVC increased compared to before treatment(both P<0.05). However, there was no significant difference in the blood flow density of FAZ, DVC, and SVC between the two groups at 1 wk, 1 and 3 mo after treatment(all P>0.05). The CRT, CMT and SFCT of the two groups at 1 wk after treatment were higher than those before treatment(all P<0.05), but there were no significant differences between the two groups(all P>0.05). The CRT, CMT and SFCT at 1 and 3 mo after treatment were lower than those at 1 wk after treatment and before treatment in both groups. The CRT, CMT and SFCT in the poor prognosis group at 3 mo after treatment were higher than those at 1 mo after treatment, and were higher than those in the good prognosis group(all P<0.05). ROC analysis showed that, at 3 mo after laser treatment in PDR patients, the area under the curve of the CRT, CMT, and SFCT alone or in combination after treatment for 1 a was 0.788, 0.781, 0.783, and 0.902, respectively, and the combined prediction value was better(P<0.05). Decision curve analysis showed that the combined detection of CRT, CMT, and SFCT in PDR patients at 3 mo after treatment can improve the predictive value of visual prognosis.CONCLUSION: The optimal time for retinal structure and function recovery in PDR patients after PRP treatment is between 1 wk and 1 mo. OCTA measurement of CRT, CMT, and SFCT at 3 mo after treatment can predict the visual prognosis during the 1 a treatment period.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Mitochondrial quality control plays an important role in maintaining homeostasis of mitochondrial network and normal function of mitochondria. ATPase family AAA domain-containing protein 3A (ATAD3A) is one of the mitochondrial membrane proteins involved in the regulation of mitochondrial structure and function, mitochondrial dynamics, mitophagy and other important biological processes. Recent studies show that ATAD3A not only interacts with Mic60/Mitofilin and mitochondrial transcription factor A (TFAM) to maintain mitochondrial cristae morphology and oxidative phosphorylation, but also interacts with dynamin-related protein 1 (Drp1) to positively/negatively regulate mitochondrial fission. In addition, ATAD3A serves as a bridging factor between the translocase of the outer mitochondrial membrane (TOM) complex and translocase of the inner mitochondrial membrane (TIM) complex to facilitate the import of PTEN-induced putative kinase protein 1 (PINK1) into mitochondria and its processing displays a pro-autophagic or anti-autophagic activity. This article reviews the role and mechanism of ATAD3A in regulating mitochondrial quality control. Firstly, as an inner mitochondrial membrane protein, ATAD3A is involved in maintaining the stability of mitochondrial crista structure, and its gene deletion or mutation will cause the loss and breakage of crista. Secondly, ATAD3A is also involved in maintaining mitochondrial respiratory function and mitochondrial nucleoid homeostasis, and its gene deletion or mutation can reduce the activity of mitochondrial respiratory chain complex and enhance the size and movement of nucleoid. Thirdly, ATAD3A participates in the negative regulation of mitochondrial fusion, but its role in mitochondrial fission may dependent on specific cell types, as it can promote and/or inhibit the mitochondrial fission by increasing and/or decreasing phosphorylation or oligomerization of Drp1. Finally, ATAD3A can interact with mitophagy-related proteins (e.g. PINK1, autophagy/beclin-1 regulator 1 (AMBRA1), acylglycerol kinase (AGK)) to enhance/reduce PINK1-Parkin-dependent mitophagy.