BACKGROUND:SOX5 is an important transcription factor of the SRY-related HMG-box(SOX)family,which plays a key role in regulating the expression of genes related to bone development and remodeling,especially during osteoblast differentiation and chondrocyte maturation,through its unique HMG box DNA structural domains in concert with SOX6 and SOX9.In addition,the expression and activity of SOX5 and its family are regulated by a variety of diseases and different forms of exercise,among other factors,suggesting that SOX5 and its family have the potential to be effective as drugs and therapeutics to ameliorate related diseases in the future.OBJECTIVE:To provide new perspectives for future research on SOX5 and to provide scientific basis for the application of exercise intervention and drug therapy in the prevention and treatment of bone diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 2001 to June 2024,and the search terms were"SRY-related HMG-box5,SOX5,Bone"in Chinese and English,respectively.After screening,analysis and summarization,105 articles were included in the final review.RESULTS AND CONCLUSION:(1)Role of SOX5 in bone development:SOX5 is an important member of the SOX family,which plays a central role in the regulation of skeletal development,bone metabolism and cartilage formation.In synergy with SOX6 and SOX9,SOX5 activates gene expression in osteoblasts and chondrocytes by binding to specific DNA sequences to regulate bone formation and bone remodeling.(2)Abnormal expression of SOX5 is closely related to bone and joint diseases such as chondrodysplasia,osteoporosis and osteoarthritis,suggesting that it may be a key regulator of these diseases.Currently,a variety of drugs may be used to treat bone metabolism-related diseases by regulating SOX5 and its family,and upregulation of SOX5 in mesenchymal stem cells may be effective in improving the symptoms of bone metabolism disease patients in bone tissue engineering.(3)Exercise may effectively prevent osteoporosis and related bone diseases by enhancing bone metabolism and promoting osteoblast differentiation and bone density increase.This mechanism of action may be related to the specific regulatory mechanism of SOX5,especially in different types,intensities and durations of exercise need to be further explored and studied.In conclusion,SOX5 has an important regulatory role in bone development,chondrogenesis,and prevention of bone diseases,and its activity is regulated by a variety of factors,while exercise intervention provides a new scientific basis for the treatment of bone diseases.

Objective To investigate the ameliorative effect and the related mechanism of rotating magnetic fields(RMF)on sevoflurane(SEV,a commonly used inhalational anesthetics in clinics)-induced cognitive impairments in elderly rats.Methods The cognitive functions of 24 elderly male SD rats which were allocated into 3 experimental groups(Control group,SEV group,and SEV+RMF group;n=8 per group)were assessedviawater maze testing,and the damage and repair of hippocampal neurons were detected using ELISA and Western blotting assays.Water maze testing was also conducted on additional 24 elderly male SD rats which were randomized into 3 groups(SEV group,SEV+RMF group,and SEV+autophagy inhibitor+RMF group;n=8 per group)for assessing their cognitive functions.Results Compared with SEV group,RMF intervention significantly reduced the escape latency and swimming distance in water maze test(P<0.01),while increasing the number of platform crossovers(P<0.001).RMF downregulated the serum levels of tumor necrosis factor-α,interleukin-1β,and interleukin-6 in SEV-treated rats(P<0.001),and led to remarkable reductions in both serum neuron-specific enolase and β-amyloid protein levels(P<0.001).Moreover,RMF upregulated the expressions of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons(P<0.001),suppressed the expression of apoptotic protein caspase-3 and autophagy related protein p62 in the hippocampus,and upregulate the expression of autophagy related protein Beclin-1(P<0.001).However,the administration of autophagy inhibitor 3-MA abolished the ameliorative effects of RMF on SEV-induced cognitive impairments in elderly rats(P<0.001).Conclusion RMF can effectively improves SEV-induced cognitive dysfunction in elderly rats,and this neuroprotective effect is mediated by the autophagy activation in hippocampal neurons.

Objective:To explore the impacts of Yiqi Wenfei Tongqiao Formula on inflammatory response and T helper cell(Th)1/Th2 immune balance in rats with lung Qi deficiency cold type allergic rhinitis.Methods:Sixty SD rats were randomly divided into model group,low dose Yiqi Wenfei Tongqiao Formula group,medium dose Yiqi Wenfei Tongqiao Formula group,high dose Yiqi Wenfei Tongqiao Formula group,and desloratadine group,with 12 rats in each group,using a combination of smoking,cold stimula-tion combined with ovalbumin(OVA)sensitization and stimulation construct lung Qi deficiency cold type allergic rhinitis model.An-other 12 normal SD rats were selected as control group.Each group of rats was treated with corresponding drugs once a day for 14 days.Model group and control group rats were given physiological saline.Scoring method was used to analyze the behavioral score and lung index of rats with allergic rhinitis.HE staining was applied to detect pathological changes in rat nasal mucosa tissue.ELISA was ap-plied to detect levels of IFN-γ,IL-4 and TNF-α in rats serum;flow cytometry was applied to detect Th1/Th2.Western blot was applied to detect expressions of T-bet and GATA-3 protein in nasal mucosa tissues of rats in each group.Results:Compared with control group,pathological damage to nasal mucosa tissue of model group rats was severe,allergic rhinitis behavior score(days 41,48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were increased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were decreased(P<0.05);compared with model group,pathological damage to nasal mucosa tissue of rats in low,medium,high doses Yiqi Wenfei Tongqiao Formula groups and desloratadine group were alleviated,the allergic rhinitis behavior score(days 48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were decreased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were increased(P<0.05).Conclusion:Yiqi Wenfei Tongqiao Formula can inhibit inflammatory response of lung Qi deficiency cold type allergic rhinitis rats By regulating Th1/Th2 immune balance.

Objective:To compare and observe the efficacy and safety of pars plana vitrectomy (PPV) combined with 41G ultrafine needle injection of balanced salt solution (BSS) and internal limiting membrane inversion and coverage in the treatment of large-diameter macular hole (MH).Methods:A prospective study. From April 2023 to April 2024, 42 patients (42 eyes) diagnosed with large-diameter MH at The Affiliated Eye Hospital of Nanchang University were included in the study. The substrate diameters (BD) of MH are all greater than 1 000 μm. All affected eyes underwent best corrected visual acuity (BCVA), microvisual field, optical coherence tomography (OCT), and OCT angiography (OCTA) examinations before surgery. BCVA examination was conducted using the international standard logarithmic visual acuity chart, and the statistics were converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity. Microfield-of-view examination records the mean retinal sensitivity (MS) within a 12° range of the fovea. The minimum diameter (MD) and BD of the hole were measured by OCT and the MH index (MHI) was calculated. OCTA measures the area and perimeter (PERIM) of the foveal avascular zone (FAZ) in the fovea centralis, as well as the retinal vessel length density (VLD) and vessel perfusion density (VPD) in the central area. The affected eyes were divided into the observation group (22 eyes, treated with PPV combined with 41G ultra-micro needle subretinal injection of BSS and the control group (20 eyes, treated with PPV combined with internal limiting membrane inversion and coverage) according to the random number table method. The patients were followed up for 6 months after the operation, and the above indicators were reexamined at 1, 3 and 6 months. The changes of BCVA, MS, FAZ parameters, VLD, VPD before and after the operation, as well as the closure of the hole and the occurrence of complications were compared between the two groups. The independent sample t test was used for comparison between groups. The correlation between postoperative indicators and preoperative structural parameters was analyzed using Pearson analysis. Results:In the 22 eyes of the observation group, the hole closure rate was 100.0% (22/22) 6 months after the operation, and the complete closure rate was 90.9% (20/22). In the control group of 20 eyes, the closure rate was 95.0% (19/20), and the complete closure rate was 90.0% (18/20). The hole closure rate of the affected eyes in the observation group was better than that in the control group, but the difference was not statistically significant ( χ2=1.736, P=0.420). The logMAR BCVA, MS, FAZ area, PERIM, VLD and VPD at each time point after the operation in both groups were significantly improved compared with those before the operation, and the differences were statistically significant ( P<0.05). The results of Pearson correlation analysis showed that in the observation group, logMAR BCVA at 6 months after surgery was positively correlated with BD before surgery ( r=0.340, P=0.029), and negatively correlated with MHI before surgery ( r=?0.350, P=0.023). Six months after the operation, MS was positively correlated with the preoperative hole height and MHI ( r=0.330, P=0.034). In the control group, 6 months after the operation, MS was negatively correlated with BD before the operation ( r=?0.480, P=0.032), and positively correlated with MHI before the operation ( r=0.510, P=0.027). Six months after the operation, the FAZ area of the affected eyes in the observation group [(0.17±0.09) mm 2] was larger than that in the control group [(0.12±0.07) mm 2], and the difference was statistically significant ( t=?0.340, P=0.025). No complications such as abnormal intraocular pressure, retinal pigment epithelium injury or retinal detachment occurred in all the affected eyes after the surgery. Conclusions:PPV combined with 41G ultra-micro needle subretinal injection of BSS for the treatment of large-diameter MH has a high rate of hole closure and good safety. Larger BD and MD, lower MHI and hole height before surgery may affect the recovery of visual function after surgery.

Objective To investigate the ameliorative effect and the related mechanism of rotating magnetic fields(RMF)on sevoflurane(SEV,a commonly used inhalational anesthetics in clinics)-induced cognitive impairments in elderly rats.Methods The cognitive functions of 24 elderly male SD rats which were allocated into 3 experimental groups(Control group,SEV group,and SEV+RMF group;n=8 per group)were assessedviawater maze testing,and the damage and repair of hippocampal neurons were detected using ELISA and Western blotting assays.Water maze testing was also conducted on additional 24 elderly male SD rats which were randomized into 3 groups(SEV group,SEV+RMF group,and SEV+autophagy inhibitor+RMF group;n=8 per group)for assessing their cognitive functions.Results Compared with SEV group,RMF intervention significantly reduced the escape latency and swimming distance in water maze test(P<0.01),while increasing the number of platform crossovers(P<0.001).RMF downregulated the serum levels of tumor necrosis factor-α,interleukin-1β,and interleukin-6 in SEV-treated rats(P<0.001),and led to remarkable reductions in both serum neuron-specific enolase and β-amyloid protein levels(P<0.001).Moreover,RMF upregulated the expressions of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons(P<0.001),suppressed the expression of apoptotic protein caspase-3 and autophagy related protein p62 in the hippocampus,and upregulate the expression of autophagy related protein Beclin-1(P<0.001).However,the administration of autophagy inhibitor 3-MA abolished the ameliorative effects of RMF on SEV-induced cognitive impairments in elderly rats(P<0.001).Conclusion RMF can effectively improves SEV-induced cognitive dysfunction in elderly rats,and this neuroprotective effect is mediated by the autophagy activation in hippocampal neurons.

Objective:To explore the impacts of Yiqi Wenfei Tongqiao Formula on inflammatory response and T helper cell(Th)1/Th2 immune balance in rats with lung Qi deficiency cold type allergic rhinitis.Methods:Sixty SD rats were randomly divided into model group,low dose Yiqi Wenfei Tongqiao Formula group,medium dose Yiqi Wenfei Tongqiao Formula group,high dose Yiqi Wenfei Tongqiao Formula group,and desloratadine group,with 12 rats in each group,using a combination of smoking,cold stimula-tion combined with ovalbumin(OVA)sensitization and stimulation construct lung Qi deficiency cold type allergic rhinitis model.An-other 12 normal SD rats were selected as control group.Each group of rats was treated with corresponding drugs once a day for 14 days.Model group and control group rats were given physiological saline.Scoring method was used to analyze the behavioral score and lung index of rats with allergic rhinitis.HE staining was applied to detect pathological changes in rat nasal mucosa tissue.ELISA was ap-plied to detect levels of IFN-γ,IL-4 and TNF-α in rats serum;flow cytometry was applied to detect Th1/Th2.Western blot was applied to detect expressions of T-bet and GATA-3 protein in nasal mucosa tissues of rats in each group.Results:Compared with control group,pathological damage to nasal mucosa tissue of model group rats was severe,allergic rhinitis behavior score(days 41,48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were increased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were decreased(P<0.05);compared with model group,pathological damage to nasal mucosa tissue of rats in low,medium,high doses Yiqi Wenfei Tongqiao Formula groups and desloratadine group were alleviated,the allergic rhinitis behavior score(days 48,56),lung index,levels of IL-4 and TNF-α,Th2 and protein expression of GATA-3 were decreased,while levels of IFN-γ,Th1,Th1/Th2,and protein expression of T-bet were increased(P<0.05).Conclusion:Yiqi Wenfei Tongqiao Formula can inhibit inflammatory response of lung Qi deficiency cold type allergic rhinitis rats By regulating Th1/Th2 immune balance.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice （APP/PS1 mice）， and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）/cysteine aspartate-specific protease （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group， MCC950 group， and Hei Xiaoyaosan high-， medium-， and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding， mice in each group were intervened. The Hei Xiaoyaosan high-， medium-， and low-dose groups were given corresponding doses by gavage （25.79， 12.90， 6.45 g·kg^-1·d^-1）， the MCC950 group was intraperitoneally injected with 10 mg·kg^-1·2 d^-1， and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention， the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining. The expression of amyloid precursor protein （APP） in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin （IL）-10， IL-18， and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 （Iba-1） in the hippocampus. Results① In the Y maze test， compared with the blank group， the spontaneous alternation rate of the model group was significantly reduced （P<0.01）. Compared with the model group， the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased （P<0.01）. ② In the Morris water maze test， during the 1-4 days of the location navigation test， the escape latency time of mice decreased with the extension of training time. On day 4， compared with the blank group， the model group showed a significantly increased escape latency （P<0.05）. Compared with the model group， the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency （P<0.05）. In the spatial exploration experiment， compared with the blank group， the number of platform crossings in the model group was significantly reduced （P<0.01）. Compared with the model group， the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings （P<0.05）. ③ HE staining showed that， compared with the blank group， the hippocampal CA3 cells of the model group were damaged， arranged loosely and irregularly， swollen， with unclear boundaries， and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that， compared with the blank group， the expression of APP in the hippocampal CA3 region was significantly increased in the model group （P<0.01）. MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice （P<0.01）. ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased， and IL-10 levels were significantly reduced （P<0.01）. Compared with the model group， the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced （P<0.01）. IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-， medium-， and low-dose groups were significantly decreased （P<0.01）. The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased （P<0.05， P<0.01）. ⑥ Western blot results showed that compared with the blank group， the protein levels of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus of the model group were significantly elevated （P<0.01）. Compared with the model group， the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased （P<0.05， P<0.01）. The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-， medium-， and low-dose groups was reduced （P<0.05， P<0.01）， and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased （P<0.05， P<0.01）. ⑦ Immunofluorescence results showed that， compared with the blank group， the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased （P<0.01）. Compared with the model group， the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced （P<0.01）. ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors， alleviate neuroinflammation，improve hippocampal histopathological changes，and improve learning and memory deficits，thus providing potential therapeutic benefits for Alzheimer's disease.

BACKGROUND:SOX5 is an important transcription factor of the SRY-related HMG-box(SOX)family,which plays a key role in regulating the expression of genes related to bone development and remodeling,especially during osteoblast differentiation and chondrocyte maturation,through its unique HMG box DNA structural domains in concert with SOX6 and SOX9.In addition,the expression and activity of SOX5 and its family are regulated by a variety of diseases and different forms of exercise,among other factors,suggesting that SOX5 and its family have the potential to be effective as drugs and therapeutics to ameliorate related diseases in the future.OBJECTIVE:To provide new perspectives for future research on SOX5 and to provide scientific basis for the application of exercise intervention and drug therapy in the prevention and treatment of bone diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 2001 to June 2024,and the search terms were"SRY-related HMG-box5,SOX5,Bone"in Chinese and English,respectively.After screening,analysis and summarization,105 articles were included in the final review.RESULTS AND CONCLUSION:(1)Role of SOX5 in bone development:SOX5 is an important member of the SOX family,which plays a central role in the regulation of skeletal development,bone metabolism and cartilage formation.In synergy with SOX6 and SOX9,SOX5 activates gene expression in osteoblasts and chondrocytes by binding to specific DNA sequences to regulate bone formation and bone remodeling.(2)Abnormal expression of SOX5 is closely related to bone and joint diseases such as chondrodysplasia,osteoporosis and osteoarthritis,suggesting that it may be a key regulator of these diseases.Currently,a variety of drugs may be used to treat bone metabolism-related diseases by regulating SOX5 and its family,and upregulation of SOX5 in mesenchymal stem cells may be effective in improving the symptoms of bone metabolism disease patients in bone tissue engineering.(3)Exercise may effectively prevent osteoporosis and related bone diseases by enhancing bone metabolism and promoting osteoblast differentiation and bone density increase.This mechanism of action may be related to the specific regulatory mechanism of SOX5,especially in different types,intensities and durations of exercise need to be further explored and studied.In conclusion,SOX5 has an important regulatory role in bone development,chondrogenesis,and prevention of bone diseases,and its activity is regulated by a variety of factors,while exercise intervention provides a new scientific basis for the treatment of bone diseases.

Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with subretinal or intravitreal injection of Conbercept for the treatment of refractory diabetic macular edema (DME).Methods:A retrospective case control study. From June 2022 to March 2024, 32 eyes of 32 patients with refractory DME diagnosed at The Affiliated Eye Hospital of Nanchang University were included in the study. There were 17 male cases with 17 eyes and 15 female cases with 15 eyes. Age was (57.44±8.99) years old; The duration of diabetes was (12.72±6.11) years. All patients had received regular treatment with anti-vascular endothelial growth factor (VEGF) drugs or corticosteroid drugs for at least 5 times, and had undergone focal retinal laser photocoagulation or panretinal laser photocoagulation, the central macular thickness (CMT) persisted or decreased by less than 50 μm. All affected eyes underwent best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), microperimetry, and laboratory glycated hemoglobin (HbA1c) testing. BCVA was measured using a standard logarithmic visual acuity chart, and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. CMT was measured using an OCT device. Microperimetry was performed using an MP-3 microperimeter, recording the mean sensitivity (MS) of the retina within a 12° range of the fovea. The affected eyes were treated with 23G PPV combined with internal limiting membrane peeling and either macular subretinal or intravitreal injection of Conbercept, and were divided into subretinal injection group and the intravitreal injection group, each consisting of 16 cases and 16 eyes. The same equipment and methods as before surgery were used for related examinations at 1, 3, and 6 months post-surgery. Changes in BCVA, CMT, and MS were observed and compared, as well as the number of additional anti-VEGF treatments required within 6 months after surgery. Intergroup comparisons were made using independent samples t tests, and repeated measures data were analyzed using repeated measures analysis of variance. Results:The age ( t=-0.271), gender composition ( χ2=0.001), duration of diabetes ( Z=-0.868), HbA1c ( t=-0.789), intraocular pressure ( t=1.689), logMAR BCVA ( t=1.393), CMT ( t=-0.613), MS ( Z=-0.132), and the number of anti-VEGF injections ( t=-0.752) between the subretinal injection group and the intravitreal injection group showed no statistically significant differences ( P>0.05). The within-subject effects comparison of BCVA, CMT, and MS at 1, 3, and 6 months post-surgery compared to pre-surgery for all affected eyes showed statistically significant differences ( F=8.060, 125.722, 39.054; P<0.05). The overall comparison of logMAR BCVA between the subretinal and intravitreal injection groups post-surgery showed no statistically significant difference ( F=0.662, P=0.422), however, comparisons of CMT ( F=4.540) and MS ( F=6.066) showed statistically significant differences ( P<0.05). At 1, 3, and 6 months post-surgery, comparisons of logMAR BCVA between the two groups showed no statistically significant differences ( t=-0.123, 0.239, 1.087; P>0.05), comparisons of CMT showed statistically significant differences ( t=-3.474, -4.832, -2.482; P<0.05), comparisons of MS showed statistically significant differences at 1 and 3 months ( t=-2.940, -2.545; P<0.05), but not at 6 months ( t=-1.527, P>0.05). At 6 months post-surgery, the number of additional intravitreal anti-VEGF injections required in the subretinal and intravitreal injection groups showed a statistically significant difference ( Z=-2.033, P=0.042). During the follow-up period and at the final follow-up, no complications such as injection site bleeding, retinal detachment, vitreous hemorrhage, macular hole, or retinal pigment epithelial tear or atrophy occurred in all affected eyes. Conclusion:Compared with intravitreal injection, subretinal injection of Conbercept for the treatment of refractory DME has more advantages in reducing macular edema and improving visual function in the macular area, and also reduces the number of postoperative anti-VEGF drug treatments.