ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

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.

Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. "Epigenetic regulation" refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
Mesenchymal Stem Cells/physiology* ; Humans ; Osteogenesis/genetics* ; Histones/metabolism* ; Cell Differentiation/physiology* ; Methylation ; Odontogenesis/genetics* ; Epigenesis, Genetic

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.

Guided by the concept of "blood-pulse-heart-spirit"， it is believed that stable angina combined with insomnia is caused by disturbance of blood vessels， which leads to loss of nourishment for the heart body and heart spirit， so the core treatment principle is to regulate the blood vessels and calm the mind. At the beginning of the disease， it shows as the liver fails to govern the free flow of qi， and disorders qi and blood； during the progress of the disease， it shows as spleen deficiency and phlegm stagnation， phlegm and blood stasis obstructing the vessels； the central mechanism of the disease shows as disturbance of blood vessels and insufficient heart yin. For the pattern of liver depression and blood stasis， pattern of phlegm and blood stasis blocking the vessels， and pattern of heart yin deficiency， it is recommended to treat by Wuzang Shenning Formula （五脏神宁方） to dredge the liver and regulate the vessels， Banxia Houpo Decoction （半夏厚朴汤） plus Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） to dissolve phlegm and regulate the vessels， and Yunpi Tiaoxin Decoction （运脾调心汤） to nourish the yin and regulate the vessels. Throughout the treatment， pattern differentiation and treatment is accompanied by the method of calming the mind with heavy sedatives and nourishing the blood to calm the mind， so as to achieve the purpose of regulating mind and heart together and treating the body and spirit at the same time.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes(T2DM).Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge.Neutral sphingophospholipase 2(Smpd3)is downregulated in jawbone-derived bone marrow mesenchymal stem cells(BMSCs)from T2DM patients.Here,we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles.The combined loading of Smpd3-overexpressing stem cell-derived exosomes(Exos-Smpd3)and nanosilver ions(Ns)to construct a hydrogel delivery system(Exos-Smpd3@Ns)promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment,ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro.Mechanistically,Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations.These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations,providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.