Characterization of peripheral blood inflammatory indicators and OCT imaging biological markers in diabetic retinopathy with or without nephropathy.

Objective: To observe the distribution characteristics of peripheral blood inflammatory indexes and retinal macular area optical coherence tomography (OCT) imaging biomarkers in patients with diabetic retinopathy (DR) with or without diabetic nephropathy (DN), in order to seek clinical biomarkers that can predict the development of DR and DN. Methods: A total of 169 inpatients with DR who visited the ophthalmology department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from October 2020 to June 2022 and had complete clinical data were collected, and the patients with DR were divided into two major groups, DR and DR/DN, according to whether they had DN, and then further divided into four subgroups, Non-proliferative DR(NPDR), proliferative DR(PDR), NPDR/DN and PDR/DN, according to the stage of DR. The distribution characteristics of peripheral blood inflammatory indexes [Neutrophil to lymphocyte ratio(NLR) and Platelet to neutrophil ratio(PLR)], renal function indexes [Cystatin-C(CYS-C), Creatinine(Crea), Uric acid(UA)and Urinary albumin to creatinine ratio(UACR)] and OCT imaging indexes [Hyperreflective foci(HRF), Disorgnization of retinal inner layers(DRIL), Outer retinal tubulations(ORTs), Central retinal thickness(CRT), Retinal nerve fiber layer(RNFL) and Ganglion cell layer(GCL)] were analyzed between the above subgroups. Results: There was no difference between DR and DR/DN groups in terms of gender, family history of diabetes, duration of diabetes and Body mass index(BMI) (P>0.05), the mean age of the DR/DN group was significantly lower than that of the DR group (P<0.05), and the proportion of the DR/DN group with a history of hypertension was significantly higher than that of the DR group (P<0.05); there was no significant difference in hemoglobin A1C(HbA1c) between DR and DR/DN groups (P>0.05). (P>0.05), Hemoglobin(HGB) was significantly higher in the DR group than in the DR/DN group (P <0.05), NLR, PLR, Crea, UA and CYS-C were significantly higher in the DR/DN group than in the DR group (P<0.05); there was no significant difference in the comparison of HRF, DRIL, ORTs positive rate and CRT between the DR and DR/DN groups (P>0.05). RNFL and GCL thickness were significantly lower in the DR/DN group than in the DR group (P<0.05); history of hypertension (OR=2.759), NLR (OR=1.316), PLR (OR=1.009), Crea (OR=1.018), UA (OR=1.004), CYS-C (OR=3.742) were the independent (OR=0.951), age (OR=0.951), HGB (OR=0.976), RNFL (OR=0.909) and GCL (OR=0.945) were independent protective factors for DR/DN; RNFL (OR=0.899) and GCL (OR=0.935) were independent protective factors for NPDR/DN, RNFL (OR=0.852) and GCL (OR=0.928) were independent protective factors for PDR/DN. ROC curve analysis showed that the area under the curve (AUC) for CYS-C, PLR, Crea, UA and the combination of the four indicators to predict DR/DN were 0.717, 0.625, 0.647, 0.616 and 0.717, respectively. Conclusions: (1) Low age combined with hypertension HGB, NLR, PLR, CYS-C, Crea and UA may be serum biological markers for predicting DN in DR; meanwhile, PLR, CYS-C, Crea, UA and the combination of the four indicators can be used for risk assessment and adjunctive diagnosis of DN in DR combined with hypertension. (2) The RNFL and GCL thickness in the temporal aspect of the central macular sulcus may be imaging biological markers for predicting DN in DR; meanwhile, GCL thickness may have important value for risk prediction and diagnosis of DN in combination with DR.

GSDMD-mediated pyroptosis in retinal vascular inflammatory diseases: a review.

PURPOSE: Pyroptosis is a newly discovered form of programmed pro-inflammatory cell death. The main signaling pathways include the classical scorch death pathway that depends on NLRP3 inflammatory vesicles and other activation caspase-1 and the non-classical scorch death pathway that depends on caspase-4 /5/11. The substrate of all inflammatory caspases is GSDMD; a large number of studies have confirmed that pyroptosis is associated with certain infectious diseases, atherosclerotic diseases, metabolic diseases, and aseptic inflammatory diseases of important organs. In recent years, pyroptosis has been studied partially in the ocular field. So, this article reviews the recent literature intending to help readers understand the main mechanisms of cellular scorch death and the progress of GSDMD-mediated cellular scorch death in retinal vascular inflammatory diseases. METHOD: A detailed review of the literature related to pyroptosis and inflammatory diseases of the retinal vasculature is presented. The following 6 electronic databases were searched: CNKI, Wanfang, VIP, PubMed, The Cochrane Library, and Embase Databases, and the search period was from the database to May 2022. The main search keywords include "Pyroptosis," " GSDMD," "Retinal Vascular Inflammatory Disease," "Diabetic retinopathy," "Retinal vasculitis." The discovery of pyroptosis, the main molecular mechanisms, key proteins, and their pathogenesis and therapeutic prospects in retinal vasculitis diseases are extensively studied and summarized. RESULT: The mechanisms of gasdermin D-mediated pyroptosis are elaborated and analyzed, with particular emphasis on their key role and potential in the pathogenesis and treatment of inflammatory retinal vascular lesions. CONCLUSION: Gasdermin D-mediated pyroptosis is a well-studied form of programmed pro-inflammatory cell death, which has a bidirectional regulatory effect on a variety of immune and inflammatory diseases. The literature reveals that pyroptosis is closely related to the pathogenesis of retinal vascular inflammatory diseases, and it may be an important therapeutic target for diabetic retinopathy and other retinal vasculitis eye diseases in the future.

The Efficacy and Safety of Dexamethasone Intravitreal Implant for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis of Randomized Controlled Trials.

Purpose: The purpose of this meta-analysis was to evaluate the efficacy and safety of dexamethasone intravitreal implant (DEX) for the treatment of diabetic macular edema (DME) with retinal vein occlusion secondary to macular edema (RVO-ME). Materials and Methods: Relevant databases were searched to include randomized controlled trials (RCTs) evaluating DEX for DME and RVO-ME. The search was conducted until March 2022. Meta-analysis was performed using Rev Man 5.4.1 software after screening the literature by inclusion and exclusion criteria, extracting information, and evaluating the methodological quality of the included studies. Results: The study showed that DEX treatment of RVO-ME was associated with an improvement in best corrected visual acuity (BCVA) (MD = -9.08, 95% CI: -10.89-7.27, P < 0.00001) and central retinal thickness (CRT) (MD = 93.47, 95% CI: 28.55-159.39, P=0.005). DEX treatment of DME was significantly better than anti-VEGF treatment in terms of CRT reduction (MD = -72.35, 95% CI: -115.0-29.69, P=0.0009). The safety study showed that the risk of cataract from RVO-ME (OR = 5.06, 95% CI: 1.96 to 13.06, P=0.0008) and the incidence of high intraocular pressure (OR = 6.67, 95% CI: 3.46 to 12.86, P < 0.00001) were significantly higher with DEX than with anti-VEGF therapy. The risk of cataract from DME (OR = 4.70, 95% CI: 2.10 to 10.54, P=0.00022) was significantly higher with DEX than with anti-VEGF therapy (OR = 4.70, 95% CI: 2.10 to 10.54, P=0.0002). The incidence of high IOP (OR = 13.77, 95% CI: 4.96 to 38.18, P < 0.00001) was significantly higher with DEX than with anti-VEGF therapy. Conclusions: In patients with DME and RVO-ME, DEX was more efficacious but slightly less safe than anti-VEGF therapy.

Neural thresholds in the diagnosis of diabetic peripheral neuropathy / 中华物理医学与康复杂志

Objective To explore the value of neural thresholds in diagnosing and treating diabetic peripheral neuropathy.Methods A total of 42 type 2 diabetics and 21 healthy counterparts were recruited,and grouped according to the patients' illness duration and level of hemoglobin A1c (HbA1C).The neural thresholds of their median,ulnar and superficial peroneal nerves were measured.Results The neural thresholds increased with the disease's duration.The average neural threshold of those living with the disease for 10 years or more was significantly higher than that with a duration of less than 10 years.The nerve thresholds also increased with the level of hemoglobin A1c(HbA1C),and they were significantly higher in the group with an HbA1C level ≥9 than those in the group with HbA1C＜9.There was a positive linear correlation between the neural threshold of the ulnar and superficial peroneal nerves and the HbA1C level (P＜0.05).However,there was no significant correlation between the neural thresholds of the median nerves and the level of HbA1C (P＞0.05).There was also a positive linear correlation between the neural thresholds of the median,ulnar and superficial peroneal nerves and the duration of the disease (P＜0.01).Conclusion The neural threshold changes with the duration of diabetes and the level of HbA1C.Evaluating the peripheral nerve function of diabetics may have clinical utility.

Protection and mechanism of bushenhuoxue on retinal ganglian cells under the hypoxic condition in vitro / 中华实验眼科杂志

Background The early disorder of diabetic retinopathy (DR) is the damage of retinal neural cells induced by high glucose and lack of oxygen.Previous studies show that bushenhuoxue serum can enhance the activity of glutamine synthetase (GS) in Müller cells under hypoxia,and glutamate-mediated retinal excitotoxicity also can be reduced by bushenhuoxue serum intervention.However,whether the concentration of glycine can be increased by bushenhuoxue serum is not clear.Objective This study was to investigate the protective effects of bushenhuoxue serum on retinal ganglion cells (RGCs) under hypoxia.Methods The Sprague Dawley (SD) rat serum containing bushenhuoxue was prepared.The RGCs of newborn SD rats were purified and identified by a twostep immunopanning procedure.After 72 hours,all RGCs were cultured in 96-well plates and divided into four groups:normal control group (cultured in adult SD rats normal serum),bushenhuoxue group (cultured in bushenhuoxue serum),hypoxia group (cultured in 1 mmol/L sodium dithionite); hypoxia + bushenhuoxue intervention group (cultured in bushenhuoxue serum+sodium dithionite).Glutamate and glycine contents in the extracellular fluid were detected by L-8800 automatic amino acid analyzer,and the content of lactate dehydrogenase (LDH) was assayed using LDH kits in 24,48 and 72 hours after culture.Results Cultured cells showed the green fluorescence under the immnofluorescence microscope.The contents of glutamate,glycine and LDH in the extracellular fluid were (0.0805±0.0010)mg/L,(0.0554±0.001 5)mg/L and (1 626.03 ±122.10)μmol/(min · L) in the normal control group in 24 hours after culture,and those in the hypoxia group were (0.022 5±0.001 1) mg/L,(0.014 6±0.001 1)mg/L and (1 458.68±94.23)μμmol/(min · L),showing significant reducing in the hypoxia group (q =-3.53,P =0.00 ; q =-2.45,P =0.00 ; q =-2.98,P =0.02).Compared with the normal control group,LDH and glycine contents in the extracellular fluid were significant raised in the hypoxia group 48 hours after culture (q =2.55,P =0.01 ;q =4.48,P =0.00).Seventy two hours after culture,the glutamate and glycine contents in the hypoxia group were higher than those of the normal control group (q =2.45,P =0.00 ;q =3.72,P =0.00).In 48 and 72 hours of culture,the contents of glycine were (0.017 4±0.001 5) and (0.019 2±0.001 2) mg/L in the hypoxia+bushenhuoxue intervention group,which were significantly higher than (0.016 0±0.001 2) and (0.018 0±0.000 8) mg/L in the hypoxiagroup (q=2.28,P=0.04;q=2.33,P=0.03),but the LDH level were (1 632.94±264.31) and (1 875.00±137.45)μmol/(min · L) in the hypoxia+ bushenhuoxue intervention group,which were lower than (1 688.49 ± 112.86) and (2 267.86 ± 175.21) μmol/(min · L) of the hypoxia group (q =-2.95,P =0.02 ; q =-2.35,P=0.00).No significant differences were seen in the glutamate content 24,48 and 72 hours after culture (P=0.55,0.28,0.46).A positive correlation was seen between the glutamate content and glycine content in the extracellular fluid (Kendall coefficient =0.519,Spearman coefficient =0.696,both at P =0.000).Conclusions The release levels of glutamate and glycine increase in the hypoxia RGCs,which probably is a compensatory response of RGCs.Bushenhuoxue serum can protect RGCs against injury by increasing the release of glycine and decreasing the LDH leakage from RGCs.

The relationship among the matrix metalloproteinase-3,carotid artery plaque and ischemic cerebrovascular disease / 中国医师杂志

Objective To investigate the relationship between the matrix metalloproteinase-3(MMP-3)and the stability of carotid artery plaque,and explore MMP-3's prediction role on the attack and relapse of acute ischemic cerebrovascular events.Methods 100 patients with the first ever acute cerebral infarction,100 patients with chronic cerebral circulation insufficiency(CCCI)and 40 persons without cerebrovascular diseases were enrolled in this study.According to the carotid ultrasound examination,100 cerebral infarction patients were divided into three subgroup: unstable plaque group(45 patients,mixed plaque,soft plaque),stable plaque group(35 patients,plaque Group)and endometrial coarse group(25patients).Matrix metalloproteinase-3(MMP-3)levels of all the subjects were measured by enzyme-linked immunosorbent assay(as basal level).All the subjects were followed up for one year to observe cerebral infarction events.Serum MMP-3 levels of each group,and the basic serum MMP-3 levels were compared among patients who were attacked or relapsed cerebral ischemic with those who had not been attack cerebral ischemic during this period of time.Results 5 patients in the cerebral infarction group had relapse (5%),2 patients in the CCCI group were attacked by cerebral ischemic(2%),and no one in the normal control group was attacked by cerebral ischemic.Serum MMP-3 levels in the acute cerebral infarction group were significantly higher than CCCI group,and both groups were significantly higher than normal control group (P ＜0.05).The basic serum MMP-3 levels in all patients who were attacked by cerebral ischemic were significantly higher than those who had not been attack by cerebral ischemic during this period of time(P ＜0.05).The serum MMP-3 levels of the unstable plaque group were significantly higher than stable plaque group.And both groups were significantly higher than endometrial coarse group(P ＜0.05).Conclusions Elevated levels of matrix metalloproteinase-3(MMP-3)might have something with the stability of carotid atherosclerotic plaque,and participate the attack and the relapse of acute cerebral infarction.Determination of MMP-3 might be used to predict the attack and relapse of acute cerebral infarction.

Serum concentrations of sCD40L in patients with acute ischemic cerebrovascular diseases / 中华全科医师杂志

One hundred patients with acute ischemic stroke were enrolled in the study as the trial group, and 20 healthy individuals as control group. Intima-media thickness and plaque of the carotis were detected by carotid ultrasonography, cerebral infarction was detected by CT/MRI, and serum concentrations of sCD40L were measured by enzyme-linked immunosorbent assay. Neurologie impairment score was evaluated in all patients. The results showed that in patients with acute ischemic stroke the serum concentrations of sCD40L in plaques group were significantly higher than those in no plaque group. The levels of serum sCD40L of infarction group (diameter>1.5 cm) were higher than those of lacunar infarction group ( diameter<1.5 cm ) and temporary ischemic attack ( TIA ) group. The levels of serum sD40L in trial group were all higher than those in control group. In the trial group, serum concentrations of sCD40L were correlated with neurologic impairment score. The results indicate that CD40/CD40L signaling pathway may be involved in the carotid atherosclerosis formation and the rupture of plaques, and the increase of serum CD40L levels might be a risk factor for acute ischemic cerebrovascular diseases.

The hemoprotective effects of a rotary magnetic field in mice exposed to irradiation / 中华放射医学与防护杂志

Objective To study the hemoprotective effects of a rotary magnetic field (RMF) to radiation-injured mice. Methods 132 male BALB/c mice were randomly divided into four groups: a normal group (N), a magnetic treatment group (M), an irradiation group(R) and an irradiation combining magnetic treatment group (R + M). Mice in the N group received no treatment. Mice in the R and R + M groups received total body irradiation with 6.0 Gy 60Co γ/rays. Mice in the M and R + M groups were treated with a RMF for one and half an hour at a time, twice a day, totally for 30 days. The survival rate was observed for 30 days. On days 0, 5, 9, 15, 21, 30, the subjects' peripheral blood cells were counted. On day 9, 23 and 30, the number of bone marrow nucleated cells (BMNCs), colony forming unit-spleen (CFU-S), spleen-body ratio, the cell cycle and apoptosis of bone marrow cells were measured. The pathological sectioning of the femur was performed and the expression level of bone morphogenetic proteins (BMP2/4) in the bone marrow was evaluated. Results ①No mice died in the N and M group. The RMF treatment increased the survival rate and survival days among the irradiated mice (P < 0.01). ②The RMF treatment increased the number of blood cells in their peripheral blood of the R + M group. ③The number of BMNCs, CFU-S and the proportation of G2 + M stage in the R + M were markedly higher than that of the R group, but the proportation of the apoptosis was lower than that of the R group on the 9th day (P < 0.05). Furthermore, the spleen index in the R + M group was also higher than that of the R group on the 23rd day (P < 0.05). ④RMF could improve the expression level of BMP2/4 in the radiation-injued mice. Conclusion The RMF treatment had an obvious protective effect against the effects of irradiation and it accelerated the recovery of hematopeiesis and the hematopoietic microenvironment in mouse bone marrow.

Relationships Between Matrix Metalloproteinase-3,High-sensitivity C-Reactive Protein and Carotid Atherosclerosis and Acute Cerebral Infarction / 国际脑血管病杂志

Objective:To investigate the relationships between matrix metalloproteinase-3 (MMP-3),high-sensitivity C-reactive protein(hs-CRP)and carotid atherosclerosis and acute cerebral infarction.Methods: Sixty-four patients with the first ever cerebral infarction and 20 normal control subjects were selected.Their serum MMP-3 levels were determined by double antibody enzyme-linked immunosorbent assays,and serum hs-CRP levels were measured by immunonephelometric assay.Their carotid intima-media thicknesses were assessed by carotid ultrasonography,and neurological deficit scores were performed in patients with acute cerebral infarction.Results:The levels of serum MMP-3 and hs-CRP in patients with acute cerebral infarction were significantly higher than those in the normal control group(P＜0.01).The levels of serum MMP-3 and hs-CRP in unstable plaque group(mixed plaque group,soft plaque group)were significantly higher than those in stable plaque group(hard plaque group)and rough intima group(P＜0.01).The levels of serum MMP-3 and hs-CRP were positively correlated with the neurological deficit scores respectively in patients with acute cerebral infarction. Conclusions:The levels of serum MMP-3 and hs-CRP in patients with acute cerebral infarction may reflect the character and stability of carotid artery plaque,and they are the important indexes in understanding the severity of cerebral infarction in clinical practice.

HPLC analysis of the constituents of Radix Puerariae absorbed into blood / 中华中医药杂志

Objective: To sieve the bioactive constituents of Radix Puerariae,serum pharmacochemistry research was performed.Method: Based on the establishment of HPLC fingerprints of Radix Puerariae,the constituents absorbed into blood were determined by comparing the HPLC fingerprints of the methanol extracts,tested serum samples and blank serum sample.Results: Four compounds absorbed into blood were detected,among which two were original constituents of Radix Puerariae(including puerarin),the other might be metabolites of the original constituents.Conclusion: These four constituents absorbed into blood were possible bioactive components of Radix Puerariae.Further studies on them will help clarify the bioactive constituents and mechanisms of Radix Puerariae.