ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Diabetic retinopathy, one of the microvascular complications of diabetes, has become a leading cause of blindness in developed countries.The disease's pathogenesis is complex and involves inflammation and oxidative stress, which eventually lead to retinal microvascular disease and neurodegenerative changes.A large body of clinical and basic research evidence shows that metformin can improve diabetic retinopathy and delay its onset and progression.Metformin exerts protective effects on retinal microangiopathy and retinal cells via AMP-activated protein kinase-dependent and -independent pathways.Metformin can improve retinal cell autophagy, apoptosis and senescence by reducing the oxidative stress response and regulating mitochondrial energy metabolism.Metformin clinical and basic research provides a new approach to treating diabetic retinopathy and a potential direction for developing drugs.This article reviews the progress of clinical and basic research on metformin's protective effects against diabetic retinopathy.

Diabetic retinopathy, one of the microvascular complications of diabetes, has become a leading cause of blindness in developed countries.The disease's pathogenesis is complex and involves inflammation and oxidative stress, which eventually lead to retinal microvascular disease and neurodegenerative changes.A large body of clinical and basic research evidence shows that metformin can improve diabetic retinopathy and delay its onset and progression.Metformin exerts protective effects on retinal microangiopathy and retinal cells via AMP-activated protein kinase-dependent and -independent pathways.Metformin can improve retinal cell autophagy, apoptosis and senescence by reducing the oxidative stress response and regulating mitochondrial energy metabolism.Metformin clinical and basic research provides a new approach to treating diabetic retinopathy and a potential direction for developing drugs.This article reviews the progress of clinical and basic research on metformin's protective effects against diabetic retinopathy.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Objective To analyze the hotspots and frontiers of researches related to pain in Parkinson's disease. Methods The literatures on pain in Parkinson's disease were retrieved from CNKI,VIP,Wanfang data,CBM and Web of Science Core Collection from inception to November,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 926 literatures were included with 293 in Chinese and 633 in English,respectively.Chinese high-fre-quency keywords were quality of life,sleep disorders and depression,while English high-frequency keywords were nonmotor symptom,quality of life and levodopa.The latest bursting word in Chinese was pathogenesis,while the latest bursting words in English were exercise and management. Conclusion Number of researches related to pain in Parkinson's disease is gradually rising,and the characteristics,patho-genesis,quality of life,rehabilitation interventions and clinical efficacy have become research hotspots.The mechanism of pain in Parkinson's disease and rehabilitation management program will be the main research top-ics in the future.

Objective To investigate the efficacy of red and blue lights combined with Yufa Shengfa solution and 5% minoxidil solution in treating Ludwig type Ⅰ female androgenetic alopecia. Methods A total of 160 patients with Ludwig type Ⅰ female androgenetic alopecia were randomly divided into group A (Yufa Shengfa solution combined with 5% minoxidil solution), group B (red and blue lights therapy combined with Yufa Shengfa solution), group C (red and blue lights therapy combined with 5% minoxidil solution) and group D (red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution), with 40 cases in each group. All the patients orally took compound glycyrrhizin tablets and Centrum multivitamins, and the therapeutic period was 3 months. Differences in hair diameter, hair density, and the number of hair follicles with multiple hairs were compared before and after treatment. Results The hair density, hair diameter, and the number of hair follicles with multiple hairs improved significantly in 4 groups compared with those before treatment, and group D showed the best improvement in these parameters, with significant between-group differences (P < 0.001). There were no serious adverse events or side effects during treatment in all the patients. Conclusion Red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution is an effective non-surgical treatment for Ludwig type Ⅰ female androgenetic alopecia.

Objective:To evaluate the accuracy, completeness, and reproducibility of domestic open-source large language models (LLM) in diabetic retinopathy (DR) patient education, and to explore their potential as intelligent virtual assistants for DR patient education.Methods:A total of 41 questions and answers related to the diagnosis and treatment of DR in five categories, namely risk factors, screening and examination, symptoms and staging, diagnosis, treatment and prognosis.All questions were repeated twice as a " new dialogue" in the LLM, and all the answers were recorded.Three senior fundus physicians independently evaluated the answers on a 6-point Likert scale for accuracy and a 3-point Likert scale for completeness and repeatability, and for each answer, the evaluator was asked to make a recommendation between the LLM and the manual answers.Five questions were randomly selected to evaluate the three open source LLM, ERNIE Bot 3.5, Qwen and Kimi chat, and the LLM with the best overall performance was selected for further evaluation in the full question bank.Results:Among the three LLM, Kimi chat had the best overall performance, Kimi chat performed best, with percentages of 6 for accuracy, 3 for completeness, and 3 for repeatability among the 5 questions at 90%, 90%, and 100%, respectively.For all questions answered, the number of words in manual replies was 106 (70, 202), which was significantly lower than 505 (386, 600) in Kimi chat ( Z=-7.866, P<0.001).There was no significant correlation between the number of Kimi chat replies and the accuracy score ( rs=-0.044, P=0.492), but it was positively correlated with the integrity score ( rs=0.239, P<0.001).The interclass correlation coefficient for accuracy and completeness scores were above 0.700 among three evaluators, with the highest agreement for repeatability at 0.853, followed by completeness of the first response at 0.771.The proportion of responses ≥5 points for accuracy was 87.0%(214/246), the proportion ≥2 points for completeness was 98.0%(241/246), and the proportion higher than 70% for repeatability was 78.5%(193/246).Kimi chat excelled in answering basic questions about the disease such as disease definition, staging, frequency of screening, and common risk factors, but performed poorly on questions involving treatment choices that require a doctor's professional judgment.The proportion of evaluators choosing Kimi chat responses as superior was 69.5% (171/246), and the reasons for non-selection included lack of characteristic answers, inclusion of too much irrelevant information, and lack of responses to questions requiring a high degree of medical expertise. Conclusions:Kimi chat answers DR-related diagnostic questions in a detailed and well-organized manner, with a high degree of accuracy, completeness and reproducibility.

Objective To compare the efficacy of ultrasound-guided microwave ablation versus thyroidectomy in the treatment of benign thyroid nodules (BTN) and to explore the influencing factors of prognosis. Methods A total of 282 BTN patients were enrolled and divided into ablation group (treated with ultrasound-guided microwave ablation, n=172) and resection group (treated with thyroidectomy, n=110) based on treatment methods. Perioperative indicators and thyroid function indices before and after surgery were compared between the two groups. Patients were followed up for 1 year and divided into good prognosis group [volume reduction rate (VRR)≥80%, n=210] and a poor prognosis group (VRR < 80%, n=72) based on the VRR. Factors influencing the prognosis of BTN patients were analyzed. Results The ablation group had shorter operative time and hospital stay, less intraoperative blood loss, and lower postoperative Visual Analogue Scale (VAS) scores compared to the resection group (P < 0.05). One month after surgery, serum thyrotropin (TSH) levels were higher, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were lower than preoperative levels in both groups, however, TSH level was lower, and FT3 and FT4 levels were higher in the ablation group compared to the resection group (P < 0.05). Univariate analysis showed that preoperative TSH levels, the proportion of solid nodules, and the proportion of nodules in the risk zone were lower, while preoperative FT4 levels were higher in the good prognosis group compared to the poor prognosis group (P < 0.05). Binary Logistic regression analysis revealed that nodule type, nodule location, preoperative TSH, and preoperative FT4 were all influencing factors for the prognosis of BTN patients (P < 0.05). Conclusion Compared to thyroidectomy, ultrasound-guided microwave ablation for BTN offers advantages such as less intraoperative blood loss, milder postoperative pain, shorter operative time and hospital stay, and less damage to thyroid function. Preoperative TSH and FT4 levels, nodule type, and nodule location are closely related to the prognosis of BTN patients and should be given attention in clinical practice.