Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

Objective To observe the effectiveness and safety of netupitant/palonosetron in the treat-ment of chemotherapy-induced nausea and vomiting(CINV)in hematologic tumor patients undergoing autol-ogous and allogeneic stem cell transplantation.Methods Adult hematologic tumor patients who received net-upitant/palonosetron to prevent chemotherapy-induced nausea and vomiting CINV during pre-transplant chemotherapy at West China Hospital of Sichuan University from January to September 2022 were collected.On the first and third day of pre-transplant chemotherapy,netupitant/palonosetron was orally administered one hour before the infusion of pre-transplant chemotherapy drugs,for a total of two doses.The nausea and CINV status of the patients from the start of pre-transplant chemotherapy to 7 days after stem cell infusion were recorded.Results As a result,a total of 125 patients with hematological tumors were included,and the complete remission rates during pre-treatment chemotherapy were 72.8%,80.0%and 66.4%in the acute phase,delayed phase,and total phase,respectively.The rates of no vomiting were 89.6%,92.0%and 72.8%,respectively.The rates of no rescue medication were 95.2%,93.6%and 73.6%,respectively.The complete remission rate of 33 plasma cell tumors and 46 leukemia and myelodysplastic syndrome patients exceeded 70%,and the complete remission rate of 46 lymphoma patients exceeded 90%.The complete response rate in the delayed phase of the pre-treatment CHiGCB regimen(chidamide+busulfan+gemcitabine+cladribine)was 93.5%,which was higher than the complete response rate of the BenMel regimen(bendamustine+mel-phalan)(72.7%)and the CHiFAB regimen(chidamide+busulfan+fludarabine+cytarabine)(71.7%).The complete remission rate during the follow-up period of the CHiGCB regimen was 91.3%,which was higher than that of the CHiFAB regimen(65.2%),with the statistically significance(P<0.05).Conclusion Netu-pitant/palonosetron can effectively control CINV in patients undergoing autologous or allogeneic hematopoiet-ic stem cell transplantation for hematologic tumors.

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

Objective:To investigate the effect of graded rehabilitation intervention on cardiac function,self-man-agement ability,exercise tolerance,sleep quality and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 125 patients with CHF admitted to Lu'an People's Hospital be-tween April 2020 and October 2023.Patients were divided into control group(n=62)and intervention group(n=63).Participants in the control group received routine rehabilitation intervention,while those in the intervention group received additional graded rehabilitation intervention.Both groups were intervened for 3 months.Cardiac function indexes,6min walking distance(6MWD),metabolic equivalent(METs),scores of exercise of self-care a-gency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS item short from health survey(SF-36),and in-cidence of adverse events during the intervention were compared between the two groups.Results:Compared to pa-tients in the control group,those in intervention group had significant lower left ventricular end-diastolic volume(LVEDV)[(108.19±2.96)ml vs.(129.51±3.34)ml],left ventricular end-systolic volume(LVESV)[(50.68±2.28)ml vs.(67.38±2.68)ml],score of Pittsburgh sleep quality index(PSQI)[(8.30±1.87)points vs.(13.99±2.06)points](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(58.17±2.08)％vs.(50.70±1.63)％],ESCA score[(148.29±19.48)points vs.(124.68±15.93)points],6MWD[(413.58±15.11)m vs.(372.22±14.62)m],METs[(6.88±0.64)kcal·kg-1·h-1 vs.(6.13±0.62)kcal·kg-1·h-1],total SF-36 score[(128.97±6.62)points vs.(104.35±5.46)points](P＜0.001 all).The inci-dence of adverse events in the intervention group was significantly lower than that in the control group(5.00％vs.18.33％,P=0.023).Conclusion:The graded rehabilitation intervention may improve the heart function,self-management ability,exercise tolerance,sleep quality and quality of life in CHF patients,and has high safety.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To investigate the effect of graded rehabilitation intervention on cardiac function,self-man-agement ability,exercise tolerance,sleep quality and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 125 patients with CHF admitted to Lu'an People's Hospital be-tween April 2020 and October 2023.Patients were divided into control group(n=62)and intervention group(n=63).Participants in the control group received routine rehabilitation intervention,while those in the intervention group received additional graded rehabilitation intervention.Both groups were intervened for 3 months.Cardiac function indexes,6min walking distance(6MWD),metabolic equivalent(METs),scores of exercise of self-care a-gency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS item short from health survey(SF-36),and in-cidence of adverse events during the intervention were compared between the two groups.Results:Compared to pa-tients in the control group,those in intervention group had significant lower left ventricular end-diastolic volume(LVEDV)[(108.19±2.96)ml vs.(129.51±3.34)ml],left ventricular end-systolic volume(LVESV)[(50.68±2.28)ml vs.(67.38±2.68)ml],score of Pittsburgh sleep quality index(PSQI)[(8.30±1.87)points vs.(13.99±2.06)points](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(58.17±2.08)％vs.(50.70±1.63)％],ESCA score[(148.29±19.48)points vs.(124.68±15.93)points],6MWD[(413.58±15.11)m vs.(372.22±14.62)m],METs[(6.88±0.64)kcal·kg-1·h-1 vs.(6.13±0.62)kcal·kg-1·h-1],total SF-36 score[(128.97±6.62)points vs.(104.35±5.46)points](P＜0.001 all).The inci-dence of adverse events in the intervention group was significantly lower than that in the control group(5.00％vs.18.33％,P=0.023).Conclusion:The graded rehabilitation intervention may improve the heart function,self-management ability,exercise tolerance,sleep quality and quality of life in CHF patients,and has high safety.

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

AIM To establish a UPLC-QTOF/MS method for the analyses of chemical constituents and constituents absorbed into blood from Qili Qiangxin Capsules by UPLC-QTOF/MS.METHODS The rats with heart failure after myocardial infarction were given intragastric administration of 0.5%CMC-Na suspension of Qili Qiangxin Capsules(crude drug dosage was 0.9 g/mL)for 4 weeks,after which blood collection was made.The analysis was performed on a 40℃thermostatic Acquity UPLC BEH C18 Column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile(positive ion manner)or water-acetonitrile(negative ion manner)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Total 151 constituents were identified,containing 38 flavonoids,36 terpenoids,23 alkaloids,11 saponins,11 phenylpropanol,10 phenolic acids,4 organic acids,4 cardiac glycosides and 14 others,along with 35 constituents absorbed into blood.CONCLUSION This accurate and stable method can provide data support for the rational clinical application of Qili Qiangxin Capsules,and lay foundation for the research on related effector substances of other Chinese traditional patent medicines.