Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

Effectiveness of 5-aminolevulinic acid photodynamic therapy in treating dissecting cellulitis of the scalp and pathological changes in skin lesions: A retrospective study.

BACKGROUND: Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS. METHODS: Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted. RESULTS: Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT. CONCLUSION: ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.

Ameliorative effect and mechanism of Sanwei ganlu on hepatic fibrosis in rats / 中国药房

OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats. METHODS The rats were randomly divided into normal group， model group， silibinin group （positive control， 50 mg/kg）， and Sanwei ganlu low-dose， medium-dose， and high-dose groups （80， 250， 800 mg/kg）. Except for normal group， hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats. Starting from the 6th week of modeling administration， they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week experiment， liver and spleen indexes of rats were calculated； the pathological structure and fibrosis changes of liver tissue were observed by HE， Masson and Sirus Red staining. The contents of alanine transaminase （ALT）， aspartate transaminase （AST）， procollagen type Ⅲ （PC Ⅲ）， collagen type Ⅳ （COL-Ⅳ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and IL-1β in serum， and hyaluronic acid （HA） and laminin （LN） in liver tissue were all detected. RESULTS Compared with the model group， the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group； the contents of ALT， AST， PC Ⅲ， COL-Ⅳ， IL-6， TNF-α and IL-1β in serum as well as the contents of HA and LN in liver tissue significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats， possibly by inhibiting the synthesis of collagen fiber， reducing transaminase content， down-regulating the levels of HA， LN， PC Ⅲ and COL-Ⅳ， and reducing the inflammatory response.

Biomarkers for predicting the severity of spinal cord injury by proteomic analysis.

Purpose: Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity. Methods: SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay. Results: After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM. Conclusion: Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.

LncRNA H19: a novel player in the regulation of diabetic kidney disease.

Diabetic kidney disease (DKD), one of the most severe complications of diabetes mellitus (DM), has received considerable attention owing to its increasing prevalence and contribution to chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, the use of drugs targeting DKD remains limited. Recent data suggest that long non-coding RNAs (lncRNAs) play a vital role in the development of DKD. The lncRNA H19 is the first imprinted gene, which is expressed in the embryo and down-regulated at birth, and its role in tumors has long been a subject of controversy, however, in recent years, it has received increasing attention in kidney disease. The LncRNA H19 is engaged in the pathological progression of DKD, including glomerulosclerosis and tubulointerstitial fibrosis via the induction of inflammatory responses, apoptosis, ferroptosis, pyroptosis, autophagy, and oxidative damage. In this review, we highlight the most recent research on the molecular mechanism and regulatory forms of lncRNA H19 in DKD, including epigenetic, post-transcriptional, and post-translational regulation, providing a new predictive marker and therapeutic target for the management of DKD.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

Dynamic evaluation of pathological changes in a mouse acne model by optical imaging technology.

Acne vulgaris is a disorder of the pilosebaceous unit that is primarily caused by hyperseborrhoea, colonization with Propionibacterium acnes, hyperkeratosis and an inflammatory response. Existing pharmacodynamic assessment methods primarily focus on a single causative factor at a certain time point, making it difficult to assess multiple factors simultaneously in real time. Therefore, it is crucial to establish a dynamic and nondestructive method for the assessment of acne in vivo. This study utilized four-dimensional optical imaging techniques to assess the pathogenic factors and pathological progression of acne. LSCI was employed to measure blood flow; TPEF was used to observe inflammatory changes (NAD(P)H) in epidermal granular layer cells and structural changes in collagen fibres in the dermal layer. Additionally, the dermatoscope was used to investigate the micro-characterization of the lesions. We observed that the epidermis in the lesion area was thickened, hair follicles were keratinized, and there was obvious inflammation and blood flow aggregation by optical imaging technology. Based on these findings, the pathological progression of this acne model could be divided into the inflammation phase, accompanied by bacterial colonization, and the reparative phase. These results provide a new perspective for the assessment of acne and offer an experimental basis for the selection of precise drugs for clinical use.

Complement and complement regulatory proteins are upregulated in lungs of COVID-19 patients.

We explored the pathological changes and the activation of local complement system in COVID-19 pneumonia. Lung paraffin sections of COVID-19 infected patients were analyzed by HE (hematoxylin-eosin) staining. The deposition of complement C3, the deposition of C3b/iC3b/C3d and C5b-9, and the expression of complement regulatory proteins, CD59, CD46 and CD55 were detected by immunohistochemistry. In COVID-19 patients' lung tissues, fibrin exudation, mixed with erythrocyte, alveolar macrophage and shed pneumocyte are usually observed in the alveoli. The formation of an "alveolar emboli" structure may contribute to thrombosis and consolidation in lung tissue. In addition, we also found that compared to normal tissue, the lung tissues of COVID-19 patients displayed the hyper-activation of complement that is represented by extensive deposition of C3, C3b/iC3b/C3d and C5b-9, and the increased expression level of complement regulatory proteins CD55, and especially CD59 but not CD46. The thrombosis and consolidation in lung tissues may contribute to the pathogenesis of COVID-19. The increased expression of CD55 and CD59 may reflect a feedback of self-protection on the complement hyper-activation. Further, the increased C3 deposition and the strongly activated complement system in lung tissues may suggest the rationale of complement-targeted therapeutics in conquering COVID-19.

Comparative study of microvascular structural changes in the gestational diabetic placenta.

AIMS: Microvascular morphology and pathological changes in gestational diabetes mellitus (GDM) placentas and normal placentas were observed via vascular casting technology, electron microscopy, and pathological detection technology. Vascular structure and histological morphology changes in GDM placentas were examined to generate basic experimental data for the diagnosis and prognostic determination of GDM. METHODS: This case-control study involving 60 placentas, 30 from healthy controls and 30 from patients with GDM. Differences in size, weight, volume, umbilical cord diameter, and gestational age were assessed. Histological changes in the placentas in the two groups were analyzed and compared. A placental vessel casting model was constructed using a self-setting dental powder technique, to compare the two groups. The placental cast microvessels of the two groups were compared using scanning electron microscopy. RESULTS: There were no significant differences in maternal age or gestational age between the GDM group and the control group (p > .05). The size, weight, volume, and thickness of the placentas in the GDM group were significantly greater than those in the control group, as was umbilical cord diameter (p < .05). Immature villus, fibrinoid necrosis, calcification, and vascular thrombosis were significantly greater in the placental mass in the GDM group (p < .05). The terminal branches of the microvessels in diabetic placenta casts were sparse, with significantly fewer ends and lower villous volume (p < .05). CONCLUSION: Gestational diabetes can cause gross and histological changes in the placenta, particularly placental microvascular changes.

Evaluation of nano-curcumin against inhaled paraquat-induced lung injury in rats.

BACKGROUND: Acute lung injury (ALI) remains a significant source of morbidity and mortality in critically ill patients and currently there is no efficient therapy for this condition. The aim of this research was to evaluate the protective activity of nano-curcumin (nano-CU) as a natural anti-inflammatory and antioxidant agent, against inhaled paraquat (PQ)-induced lung injury. METHODS: One group of rats was exposed to saline (control group, Ctrl) and six groups to PQ aerosol (54 mg/m3 on alternate days 8 times, each time for 30 min) treated with drinking water alone (group PQ), 2 and 8 mg/kg nano-CU (nano + CU(L) and nano + CU(H)), 5 mg/kg pioglitazone (PIO), nano-CU(L) + PIO or 0.03 mg/kg dexamethasone (Dexa) for 16 days after PQ exposure period. PIO and Dexa were intraperitoneal (ip) injected and nano-CU was administered orally (po), (6 rats in each group). RESULTS: In the PQ group, total and differential WBC counts, malondialdehyde (MDA) in the bronchoalveolar lavage fluid (BALF), interferon gamma (INF-γ) and interleukin 10 (IL-10) levels in the lung tissues, lung pathological changes, and tracheal responsiveness were increased but the BALF thiol, catalase (CAT) and superoxide dismutase (SOD) levels were reduced. In treated groups with nano-CU(H) and PIO + nano-CU(L), all measured variables, in Dexa and nano-CU(L) treated groups, most variables and in the PIO group only a few variables were improved. The improvement of most variables in the PIO + nano-CU(L) group was significantly higher than in the PIO and nano-CU(L) groups alone. CONCLUSIONS: Nano-CU ameliorated lung damage induced by inhaled PQ similar to dexa and a synergic effect between nano-CU and PIO was observed, suggesting, a possible PPAR-γ receptor-mediated effect of curcumin.

Pathological changes in the brain after peripheral burns.

Brain injuries are common complications in patients with thermal burns and are associated with unpleasant outcomes. In clinical settings, it was once believed that brain injuries were not major pathological processes after burn, at least in part due to the unavailability of specific clinical manifestations. Burn-related brain injuries have been studied for more than a century, but the underlying pathophysiology has not been completely clarified. This article reviews the pathological changes in the brain following peripheral burns at the anatomical, histological, cytological, molecular and cognitive levels. Therapeutic indications based on brain injury as well as future directions for research have been summarized and proposed.

Choroidal Microvasculature Dropout in Glaucoma.

Glaucoma is a group of diseases characterized by distinctive visual field defect and optic nerve atrophy usually associated with elevated intraocular pressure (IOP). It is one of the most serious visual disorders and the leading cause of irreversible blindness worldwide. As a multifactorial disease, the pathogenesis of glaucoma is complicated and has been far from fully understood, where vascular factors are recognized to play an important role in its development and progression of glaucoma. Empirical researches have shown that parapapillary choroidal microvasculature dropout (CMvD) is closely associated with the impairment of optic nerve head (ONH) perfusion, probably accelerating the progression of glaucoma. Accordingly, it is necessary to explore the details regarding the relationship between CMvD and glaucoma progress, hoping to enhance the understanding of pathogenesis of glaucoma. In this review, we aimed to establish comprehensive understanding of the relationship between CMvD and glaucoma with generally going through relevant up-to-date literatures. Among the events that are closely associated with CMvD, we summarized the ones specifically involved in the term of glaucomatous pathological process, including thickness of retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) morphology, cricumpapillary vessel density (cpVD) and visual function such as visual field (VF) defect as well as the prognosis of glaucoma. Although researchers have made great advances, there are still many issues need to be addressed particularly concerning the pathogenic role of CMvD in glaucoma development and its clinical implications with respect to glaucoma prognosis.

Sub-chronic ammonia exposure induces hepatopancreatic damage, oxidative stress, and immune dysfunction in red swamp crayfish (Procambarus clarkii).

Ammonia, as one of the primary water pollutants in aquaculture, has been shown to induce a wide range of ecotoxicological effects on aquatic animals. In order to investigate the antioxidant and innate immune responses in crustaceans disrupted by ammonia, red swamp crayfish (Procambarus clarkii) were exposed to 0, 15, 30, and 50 mg/L total ammonia nitrogen for 30 d, the alterations of antioxidant responses as well as innate immunity were studied. The results showed that the severity of hepatopancreatic injury were aggravated by the increasing ammonia levels, which were mainly characterized by tubule lumen dilatation and vacuolization. The swollen mitochondria and disappeared mitochondria ridges suggested that oxidative stress induced by ammonia targets the mitochondria. Concurrently, enhanced MDA levels, and decreased GSH levels as well as the decreased transcription and activity of antioxidant enzymes, including SOD, CAT, and GPx were noticed, which suggested that high concentrations of ammonia exposure induce oxidative stress in P. clarkii. Furthermore, a significant decrease of the hemolymph ACP, AKP, and PO along with the significant downregulation of immune-related genes (ppo, hsp70, hsp90, alf1, ctl) jointly indicated that ammonia stress inhibited the innate immune function. Our findings demonstrated that sub-chronic ammonia stress induced hepatopancreatic injury and exert suppressive effects on the antioxidant capacity as well as innate immunity of P. clarkii. Our results provide a fundamental basis for the deleterious effects of ammonia stress on aquatic crustaceans.

Tilapia lake virus (TiLV) causes severe anaemia and systemic disease in tilapia.

Tilapia lake virus disease (TiLVD) is an emerging disease in tilapia that is associated with mass mortality affecting global tilapia aquaculture. In this study, red hybrid tilapias (Oreochromis spp.) were experimentally infected by intracoelomic injection with Tilapia lake virus (TiLV) to gain a better understanding of the clinicopathological changes during infection. Pale bodies and gill were observed in infected fish after 7 days of post-challenge (dpc) associated with severe anaemia. Further haematological analysis in TiLV-infected fish revealed decreased levels of haemoglobin and haematocrit at 3 dpc. Common pathological findings included pale and friable liver, pale intestine with catarrhal content, and dark and shrunken spleen in TiLV-infected fish at 7 dpc and 14 dpc. Histologically, reduced numbers of red blood cells and accumulation of melano-macrophage centre in the spleen were found in infected fish at 3 dpc, and severe lesions were more commonly observed at 7 and 14 dpc. Lymphocyte infiltration, syncytial cell formation and multifocal necrotic hepatitis were the prominent pathological findings in the liver of infected fish. The severity of pathological changes was associated with TiLV-infection with higher viral loads and with the expression pattern of pro-inflammatory cytokines and antiviral genes, including interferon regulatory factor 1 (irf1), interleukin (il-8), radical s-adenosyl methionine domain containing 2 (rsad2) and mx. Our study provides a comprehensive analysis of the haematological profile and pathological changes in tilapia during TiLV infection. Overall, lesions present in various organs, together with alteration of host immune response in TiLV-infected fish, indicate the systemic infection of this virus. The knowledge gained from this study improves our understanding of how TiLV causes pathological and haematological changes in tilapia.

Artificial Infestation of Sarcoptes scabiei (Acari: Sarcoptidae) in Rabbits Exhibits Progressive Pathological Changes, Apoptosis, and Keratinization in the Skin.

Sarcoptes scabiei (S. scabiei) is an ectoparasite that can infest humans and 150 mammalian host species, primarily causing pruritus, crust, and alopecia. However, neither the pathological process of host skin under S. scabiei infection nor the mechanism of S. scabiei infection in regulating apoptosis and keratinization of host skin has been studied yet. In this study, a total of 56 rabbits were artificially infested with S. scabiei, and the skin samples were collected at seven different time points, including 6 h, 12 h, day 1, day 3, 1 week, 4 weeks, and 8 weeks, whereas a group of eight rabbits served as controls. We measured epidermal thickness by H&E staining, observed the skin ultrastructure by electron microscopy, and detected the degree of skin apoptosis by TUNEL staining. The level of transcription of genes related to apoptosis and keratinization was detected by quantitative real-time PCR (qRT-PCR), and the level of Bcl-2 protein expression was further detected using immunohistochemistry. Our results showed that, with increased infestation time, the epidermal layer of the rabbit skin exhibited significant thickening and keratinization, swollen mitochondria in the epidermal cells, and increased skin apoptosis. The level of caspase-1, 3, 8, 10, 14, and Bcl-2 mRNA expression was increased, whereas the level of keratin 1 and 5 was decreased after S. scabiei infestation. In conclusion, S. scabiei infestation causes thickening of the epidermis, which may be related to apoptosis-induced proliferation and skin keratinization.

CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability.

Transient focal ischemia decreased microRNA-7 (miR-7) levels, leading to derepression of its major target α-synuclein (α-Syn) that promotes secondary brain damage. Circular RNA CDR1as is known to regulate miR-7 abundance and function. Hence, we currently evaluated its functional significance after focal ischemia. Transient middle cerebral artery occlusion (MCAO) in adult mice significantly downregulated both CDR1as and miR-7 levels in the peri-infarct cortex between 3 and 72 h of reperfusion. Interestingly, neither pri-miR-7a nor 7b was altered in the ischemic brain. Intracerebral injection of an AAV9 vector containing a CDR1as gene significantly increased CDR1as levels by 21 days that persisted up to 4 months without inducing any observable toxicity in both sham and MCAO groups. Following transient MCAO, there was a significant increase in miR-7 levels and CDR1as binding to Ago2/miR-7 in the peri-infarct cortex of AAV9-CDR1as cohort compared with AAV9-Control cohort at 1 day of reperfusion. CDR1as overexpression significantly suppressed post-stroke α-Syn protein induction, promoted motor function recovery, decreased infarct size, and curtailed the markers of apoptosis, autophagy mitochondrial fragmentation, and inflammation in the post-stroke brain compared with AAV9-Control-treated cohort. Overall, our findings imply that CDR1as reconstitution is neuroprotective after stroke, probably by protecting miR-7 and preventing α-Syn-mediated neuronal death.

Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results.

BACKGROUND: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. MATERIALS AND METHODS: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. RESULTS: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0-65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 (p = 0.001) and with NA (p = 0.001). CONCLUSIONS: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.

Diabetes mellitus and its influence on the incidence and process of diabetic retinopathy.

OBJECTIVES: The main aim of the study was to show the effect of diabetes in relation to the gender of the patients, duration of the disease, and on the incidence of diabetic retinopathy. In this study, we investigated the prevalence of these two diseases, pathological ocular changes and progression of disease occurrence in relation to the duration of the disease with respect to their impact on the quality of vision of the patient. METHODS: The prospective observational cross-sectional study included 3,951 patients (1,838 males, 2,113 females) with diabetes mellitus from 7 districts of eastern Slovakia. Patients with diabetes mellitus and diabetic retinopathy were identified by special screening in the number of 2,093 (1,094 females and 999 males). Subjects were divided by sex and by duration of diabetes into 5 groups: patients with diabetes under 5, 10, 15, 20, and over 20 years. We differentiated between proliferative and non-proliferative forms of diabetic retinopathy and monitored changes in visual quality. Manifestations of pathological changes were recorded using special examination methods in the eye clinic. We observed a decrease in vision by two lines, pathological changes on the retina and the occurrence of practical blindness. RESULTS: Of the total number of diabetic patients examined, diabetic retinopathy was also present in more than half of the patients. The major form represented in the patients was the non-proliferative form of retinopathy. The obtained results confirmed that the representation of patients with diabetic retinopathy increases with increasing duration of diabetes. Similarly, pathological changes characteristic of this type of late complication of diabetes were also more frequent, such as deterioration of visual acuity, the appearance of aneurysms, hard exudates macular edema, and gradual loss of vision, which can result in practical blindness. CONCLUSION: The percentage of people with diabetic retinopathy increases with the duration of diabetes, as well as the increased frequency of pathological late complication of diabetes, including deterioration of visual acuity, the development of aneurysms, hard exudates, macular oedema, and gradual loss of vision, which can result in practical blindness. Early diagnosis of the disease and introduction of appropriate treatment would alleviate the symptoms of the disease in more than half of the patients, so more frequent preventive check-ups with an ophthalmologist should be performed in diabetic patients to avoid detection of the disease in its late stages.

Analysis of Mechanism of Qinggan Jianpi Huoxue Prescription in Treatment of Hepatic Fibrosis Rats by Regulating M1/M2 Macrophages / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription（QGJPHXP） on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride（CCl4）. MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl4-olive oil suspension twice a week at the dosage of 2.0 mL·kg-1 for 8 weeks. After the model was successfully established， these rats were randomly divided into the model group， QGJPHXP group（32.084 g·kg-1） and Biejiajian pills（BJJP） group（0.925 5 g·kg-1）， with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose， and the blank and model groups were given the same dose of purified water， once a day. After 4 weeks of continuous administration， the liver tissues of rats were taken and stained with hematoxylin-eosin（HE） and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels. Interleukin（IL）-6， IL-12， IL-10， IL-1β， transforming growth factor-β1（TGF-β1） and tumor necrosis factor-α（TNF-α） levels in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）. The expression levels of CD86 and CD206 were detected by immunohistochemistry（IHC）. Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase（iNOS）， arginase-1（Arg-1）， phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK）， nuclear transcription factor-κB p65（NF-κB p65） in liver tissues of rats. ResultCompared with the blank group， the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed， while the serum levels of ALT and AST were significantly increased in the model group（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β1， TNF-α， CD86， CD206， iNOS， p-p38 MAPK，p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased（P<0.05， P<0.01）， while the levels of IL-10 and Arg-1 were obviously decreased（P<0.05， P<0.01）. Compared with the model group， QGJPHXP group reduced the degree of liver cell fibrosis，and serum levels of ALT and AST（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β1， TNF-α， CD86， iNOS， p-p38 MAPK， p38 MAPK， and NF-κB p65 levels in liver tissues were obviously decreased（P<0.05， P<0.01）， the levels of IL-10， CD206 and Arg-1 were obviously increased in the QGJPHXP group（P<0.05， P<0.01）. ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages， induce the secretion of anti-inflammatory cytokines by M2 macrophages， reduce the release of pro-fibrogenic cytokines， and promote the macrophage polarization of M1 to M2 in liver for tissue repair， thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug.