Diabetic retinopathy(DR)is one of the most common and serious microvascular complications of diabetes, posing a significant threat to patients' visual health. In recent years, epigenetic mechanisms have garnered increasing attention in the scientific community for their pivotal role in the onset and progression of DR. This paper systematically examines the regulatory roles of epigenetic mechanisms in DR, covering key pathways such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Under hyperglycemic conditions in diabetes, these epigenetic mechanisms modulate gene expression, thereby influencing critical pathological processes such as oxidative stress, inflammatory responses, mitochondrial dysfunction, and metabolic memory. This article reviews recent advances in epigenetic regulation in DR, providing an in-depth analysis of its underlying molecular mechanisms and complex regulatory networks, and explores the potential of epigenetic markers as diagnostic biomarkers and therapeutic targets. Additionally, this article highlights emerging therapeutic strategies targeting epigenetic modifications, aiming to provide a theoretical foundation and research direction for the early diagnosis and precision treatment of this disease.

OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats.

To investigate the prevalence and associated factors of fall risk among Chinese older adults, and to examine the roles of urban-rural differences, regional disparities, physical health status, and psychosocial factors in falls among this population, thereby providing evidence for tailored fall prevention strategies.

Based on the data from the 5^th National Physical Fitness Surveillance in China, this study aimed to explore the relationship between abnormal body weight and physical fitness levels in older adults.

To explore the dose-response correlation between appendicular skeletal muscle index (ASMI) and muscle strength in older adults.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To investigate the effect of type 2 taste receptor(T2R)38 activation on ferroptosis of human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and to clarify its possible mechanism.Methods:The human airway epithelial NuLi-1 cells were divided into control group(without any treatment),cigarette smoke extract(CSE)group(treated with 5％CSE for 24 h)and CSE+T2R38 specific agonist phenylthiocarbamide(PTC)group(CSE+PTC group)(treated with 5％CSE and 1 mmol·L-1 PTC for 24 h).The expression levels of T2R38 mRNA and protein in NuLi-1 cells in various groups were determined by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The cell viabilities in various groups were determined by cell counting kit-8(CCK-8)assay.The activities of inducible nitric oxide synthase(iNOS),endothelial nitric oxide synthase(eNOS),and superoxide dismutase(SOD)in the cells in various groups were measured by kits.DAX-J2 red fluorescence probe was used to determine the levels of nitric oxide(NO)in the cells in various groups.The reactive oxygen species(ROS)levels in the cells in various groups were detected by fluorescent probe kit.The levels of malondialdehyde(MDA),Fe2+,and reduced glutathione(GSH)in the cells in various groups were determined by enzyme-linked immunosorbent assay(ELISA)method.Western blotting method was used to determine the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and glutathione peroxidases 4(GPx4)proteins in the cells in various groups.Results:Compared with control group,the expression levels of T2R38 mRNA and protein in NuLi-1 cells in CSE group were increased(P＜0.05).Compared with control group,the viability of NuLi-1 cells in CSE group was decreased(P＜0.05),the activities of iNOS and SOD in cells in CSE group were increased(P＜0.05),the levels of NO and ROS were increased(P＜0.05),the levels of MDA and Fe2+were increased(P＜0.05),and the GSH level and the expression levels of Nrf2 and GPx4 proteins were decreased.Compared with CSE group,the viability of NuLi-1 cells in CSE+PTC group was increased(P＜0.05),the activity of SOD and the GSH level in the cells were increased(P＜0.05),the activity of iNOS in cells was decreased(P＜0.05),the levels of NO and ROS in cells were decreased(P＜0.05),the levels of MDA and Fe2+were decreased(P＜0.05),and the expression levels of Nrf2 and GPx4 proteins were increased(P＜0.05).There was no significant difference in eNOS activity among control group,CSE group,and CSE+PTC group(P＞0.05).Conclusion:Activation of bitter taste receptor T2R38 can inhibit ferroptosis in human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and its mechanism may be related to the reduction of iNOS activity in the cells.

OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

Objective:To investigate the safety and efficacy of urinary microbiota transplantation（UMT）in treating interstitial cystitis（IC）.Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women（45，62，79 years）presented with urinary frequency（10 - 90 min intervals），urgency，dysuria，lower abdominal pain，and non-organic sleep disorder，with nocturia（2 - 15 episodes）causing sleep difficulty. Disease durations were 3，6，and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture（x2）ruled out bacterial cystitis，and diagnosed as interstitial cystitis（IC），with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale（SDS）of 49，self-rating anxiety scale（SAS）of 31，interstitial cystitis symptom index（ICSI）of 5，interstitial cystitis problem index（ICPI）of 2，brief urological problem scale of 50，genitourinary pain assessment scale of 10，and pain catastrophizing scale（PCS）of 0. For case 2，the scores were 60 of SDS，66 of SAS，9 of ICSI，11 of ICPI，50 of brief urological problem scale，28 of genitourinary pain assessment scale，and 34 of PCS. For case 3，the scores were 44 of SDS，48 of SAS，11 of ICSI，5 of ICPI，33 of brief urological problem scale，27 of genitourinary pain assessment scale，and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage（Case 1），numerous spots（Case 2），and distinct sheets（Case 3）. Preoperative urine 16S rRNA sequencing revealed low diversity，increased Gardnerella/ Bacteroides（opportunistic），and decreased Bacillus/ Streptococcus（beneficial）. Two healthy young female donors had normal comprehensive tests covering blood/urine/stool，coagulation，CRP，immunity，liver/kidney function，lipids，infectious diseases，hormones，tumor markers，urine culture，TOUCH，and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic（ Gardnerella/ Bacteroides）abundance. Donor midstream morning urine was catheter-collected，centrifuged，and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day，donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment，scale scoring，cystoscopy evaluating mucosal inflammation，hydrodistension checks，and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief，scale score reduction，and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction；three reported relief from urinary frequency/urgency on postoperative day 7，with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria（e.g.， Cupriavidus，Ureaplasm，Mycobacterium，Pseudomonas）and an increase in the abundance of beneficial bacteria（ Dietzia，Halomonas，and Streptococcus），and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months，and the lab tests were normal，with SDS scales of 38，SAS of 20，ICSI of 3，ICPI of 2，brief urological problem scale of 44，genitourinary pain assessment scale of 10，PCS of 0，at 9 months post-op follow-up，indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation，which improved versus preoperative situation. Case 2 was followed up for 15 months，and the lab tests were normal，with SDS scales of 44，SAS of 34，ICSI of 4，ICPI of 2，brief scale of urinary problems of 0，genitourinary pain assessment scale of 9，PCS of 7，at 2 months post-op follow-up，showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months，with an increased leukocytes of urine and the other being normal for lab tests，and SDS scales of 35，SAS of 46，ICSI of 13，ICPI of 13，brief scale of urinary problems of 10，genitourinary pain assessment scale of 33，PCS of 11，at 13 months post-op follow-up，indicating physical and mental improvement. The hydro-distention revealed mucosal congestion，marked submucosal vasodilation，and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency，urgency，and pain in IC patients with sustained effects，significantly improves urine microecology，and shows no adverse events，positioning it as a viable intervention for IC.