Diabetic Retinopathy (DR) is a chronic, progressive and potentially harmful retinal microvascular disease that is associated with persistent hyperglycemia.Without timely and effective treatment, it will seriously damage the vision of patients and bring great inconvenience to their lives.The development of DR involves various mechanisms such as blood-retinal barrier damage, inflammation and neurodegeneration.Intraocular fluids, including aqueous humor and vitreous fluid, can directly reflect the changes in the intraocular environment and have a good indication of the progress of intraocular lesions.In recent years, the changes of various cytokines in intraocular fluid during the occurrence of DR and their influence on the disease course and their changes after treatment have been widely studied.This article focuses on the changes in angiogenesis-related cytokines such as vascular endothelial growth factor, placental growth factor, galectin-1, angiotensin 1 (Ang1), Ang2 and inflammation-related cytokines such as tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, transforming growth factor-β, interleukin (IL)-1β, IL-6, IL-8, IL-10 in the intraocular fluid of DR patients, and the changes of these cytokines and the significance after treatment in patients with diabetic macular edema and proliferative DR to provide potential targets for exploring new and personalized clinical treatment and theoretical basis to improve the prognosis of patients with DR.

Objective:To compare the effect of uPWS R15 software based on deep learning with MIM-Maestro 6.9 software based on atlas library to automatically delineate the organs at risk of prostate cancer in order to provide a reference for clinical application.Methods:The CT data of 90 prostate cancer patients admitted to the Department of Oncology Radiotherapy of the Affiliated Hospital of North Sichuan Medical College from 2018 to 2022 were retrospectively selected. Based on the uPWS R15 software developed by Shanghai United Imaging Medical Technology Company and the MIM-Maestro 6.9 software developed by Beijing Mingwei Vision Medical Software Company, the effects of uPWS and MIM software on automatic delineation of organs at risk were evaluated according to five parameters, including delineation time (T), Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), Hausdorff distance (HD) and the mean distance to agreement (MDA).Results:The sketching time of uPWS software was less than that of MIM software. There were no significant differences in the sketching effect of femoral head and skin between the two software (all P>0.05). The delineation of right kidney ( tMDA=-3.43, zDSC=-4.03, zJSC=-4.16, P<0.05), left kidney ( tMDA=-3.87, zDSC=-4.18, zJSC=-4.41, P<0.05), small intestine ( tMDA=-8.57, zDSC=-9.99, tJSC=14.21, P<0.05) and rectum ( zMDA=-4.00, tDSC=-9.98, tJSC= 9.72, P< 0.05) except HD, was statistically different. The bladder ( z=-7.88, -9.00, -8.17, -8.74, P<0.05) and spinalcord ( z=-3.87, -4.43, 4.03, 3.05, P<0.05) were also delineated with significant differences. The DSC automatically delineated by uPWS software was >0.7, while the DSC automatically delineated by MIM software was >0.7 for all other organs at risk except small intestine and rectum. In addition, the HD, MDA and JSC values of the organs at risk (bilateral femoral head, bilateral kidneys, spinal cord, bladder, skin, rectum and small intestine) automatically delineated by uPWS software were generally better than those with MIM software. Conclusions:The uPWS software outlines better than the MIM software, but the MIM software can also be used clinically with modifications to the small bowel and rectum, saving a great deal of time in preparation for radiation therapy.

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

ObjectiveTo explore the application value of CT pulmonary angiography (CTPA) in assessing the severity of acute pulmonary embolism (APE) and right heart function in rehabilitation patients. MethodsFrom January, 2013 to January, 2020, 133 inpatients (94 positive and 39 negative) who underwent CTPA examination in Beijing Bo'ai Hospital were involved. Positive patients were further divided into mild, moderate and severe groups based on the pulmonary artery obstruction index (PAOI). The clinical parameters and right heart function indicators were compared. Spearman correlation analysis was used to analyze the correlation between PAOI, and clinical parameters and right heart function indicators, and Logistic regression analysis was used to predict the risk factors of APE. ResultsThere was significant difference in lower extremity venous thrombosis, D-dimer, oxygen partial pressure, PAOI and left process of interventricular septum among four groups (H ≥ 12.350, P < 0.01). PAOI was moderately positively correlated with D-dimer (r = 0.443, P < 0.001) and left process of interventricular septum (r = 0.520, P < 0.001), and was weakly positively correlated with lower extremity venous thrombosis (r = 0.399, P < 0.001), left pulmonary artery diameter (r = 0.213, P = 0.014) and inferior vena cava regurgitation (r = 0.229, P = 0.008). Lower extremity venous thrombosis (OR = 7.708, P < 0.001) and left process of interventricular septum (OR = 3.641, P = 0.008) were independent risk factors for the onset of APE. The combination of the two indicators was effective for diagnosis of APE, and AUC was 0.795 (95% CI 0.715 to 0.874). ConclusionCTPA may be applied to evaluate the severity of APE and right heart function in rehabilitation patients.

Objective:This work aims to assess the distribution of peripheral blood monocyte subsets, the expression level of the functional markers in rheumatoid arthritis (RA) patients, and analyze the correlation between the above indexes and the onset of RA.Methods:Peripheral blood mononuclear cells were collected and isolated from 62 RA patients, 52 healthy control (HC) and 12 disease control group′s patients via density centrifugation. The enrolled patients were attended or underwent physical examination in East Hospital, Tongji University from June 2020 to December 2021. Monocytes could be classified into classical (CM), intermediate (IM) and non-classical (NCM). Then, the flow cytometry was performed to examine the distribution of monocyte subsets and the measure the expression level of human leukocyte antigen DR (HLA-DR), intracellular tumor necrosis factor α (TNF-α) in peripheral blood monocytes. The statistical methods in this study mainly include: Kruskal-Wallis H test, Chi-Square test, Mann-Whitney U test, Wilcoxon matched-pairs signed ranks test, Spearman correlation coefficient test and Logistic regression analysis. The diagnostic value of IM proportion in RA was analyzed by ROC curve. Results:The monocytes number and monocytes proportion in white blood cells were much higher in RA [0.40 (0.40, 0.50), 7.60% (5.97%, 8.53%)] and disease control [0.40 (0.40, 0.68), 8.20% (5.85%, 10.28%)] compared with HC [0.30 (0.30, 0.40), 5.80% (5.03%, 6.38%)] ( H=24.733, P<0.001; H=27.469, P<0.001). A statistic-significant difference was detected among the proportion of CM[85.49%(76.91%,89.21%),88.94%(86.36%,91.72%),90.26%(80.25%, 92.56%)],IM[11.65%(8.47%,17.89%),7.89%(5.36%,10.75%), 5.56%(4.17%, 8.27%)], NCM[2.22%(1.39%, 3.74%), 2.49%(1.74%, 4.66%), 5.13%(3.39%, 9.85%)] in RA group, HC group and disease control group ( H=11.389, P=0.003; H=20.815, P<0.001; H=10.640, P=0.005). The proportion of CM was lower in RA and the IM proportion was increased in RA( P=0.003; P=0.003). The intracellular TNF-α level of monocytes in all three groups revealed the trend that IM>NCM>CM. The intracellular TNF-α in IM of RA was positively associated with serum TNF-α ( r=0.376, P=0.041). The HLA-DR expression in IM subsets were higher than CM and NCM subsets in all RA,HC and disease control groups. The expression of HLA-DR of IM in RA group and disease control was higher than HC group [8 611.50 (6201.3, 9890.8), 10 295.0 (7 899.0, 13632.0), 6 278.00(4 057.8, 9522.0), H=10.495, P=0.005]. There were no correlations between the proportion of peripheral blood IM and clinical characteristics CRP ( r=0.119, P=0.359), RF ( r=0.204, P=0.112) and ESR ( r=0.153, P=0.236). Logistic regression analysis showed that the proportion of IM ( OR=1.169, 95% CI 1.003-1.363, P=0.046), CRP ( OR=1.277, 95% CI 1.000-1.631, P=0.050), RF ( OR=1.179, 95% CI 1.080-1.287, P<0.001) are positively correlated with RA onset. The area under ROC curve for diagnosis of RA with IM proportion was 0.687, and the 95% confidence interval was 0.590-0.784, P<0.001. Conclusions:The distribution of monocyte subsets in peripheral blood of RA patients is abnormal. The increase in the proportion of IM, the enhanced antigen-presenting ability, and the increased level of TNF-α secretion in RA patients may play an important role in the pathogenesis of RA.

Objective:To formulate sustainable development strategies for the newly-found clinical science and technology innovation park to improve the clinical research and disease diagnosis and treatment.Methods:PEST-SWOT model was used to analyze the internal and external environmental factors that impact the development of the park.Results:The advantages and disadvantages of the park were analyzed as well as the opportunities and challenges. Effective strategies for the construction and development of the park were put forward from four aspects, such as SO, ST, WO and WT.Conclusions:The development strategy proposed in this study is conducive to establish a well-known clinical science and technology innovation park which is an institute integrating clinical and scientific research.

Background: Metabolic diseases pose considerable burden on the healthcare system worldwide, indi-cating the significance of prevention and treatment. In constitution theory of traditional Chinese med-icine, phlegm-dampness constitution (PDC) is the common basis of metabolic diseases. In clinical practice, Huatan Qushi (HTQS) decoction targeting on PDC can effectively improve metabolic indicators. However, its underlying biochemical mechanism still remains unclear.Methods: Eight PDC participants received HTQS decoction for three months. Their blood was collected at baseline and 1 and 3 months after intervention started. Related biomedical indicators were detected. High-throughput sequencing and RT-qPCR were used for validation. Due to the missing data, repeated measures with missing values in mixed models were used. Results: After 3-month treatment, HDL-C level increased (P<.001) and FBG, FINS, and HbA1c all showed decreasing trend at different time points (all P < .05). After miRNA high-throughput sequencing, compared with the baseline, differential miRNAs at 1 and 3 months were screened, and target gene prediction and KEGG pathway enrichment analysis were performed. The results displayed that metabolic disease-related pathways mainly included pathways in cancer, PI3K-Akt signaling pathway, etc. Further, RT-qPCR showed that hsa-miR-1237-3p differed statistically (P =.008). Then we validated the target genes of hsa-miR-1237-3p in the"Pathways in Cancer"pathway including SDF1, AC, CRK, and HGF, also known as upstream target genes of PI3K/AKT pathway. The results showed that two indicators of CRK and HGF were in statistical significance (P=.045 and P=.036, respectively). Conclusion: PDC serves as a common basis for various metabolic diseases. Through adjusting PDC, HTQS decoction can improve biomedical indicators including blood glucose, HbA1c, insulin, and HDL-C. The target pathway is"Pathways in cancer". Specifically, HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237-3p, and probably exerts effects on their downstream PI3K/AKT pathway.

Objective: To investigate the clinical and pathological features of ischemia renal injury. Methods: Patients with biopsy-proven ischemia renal injury in the Department of Nephrology, Peking University First Hospital from 2010 to 2018 were retrospectively enrolled in the present study. The demographic information and laboratory data were collected. And the severity of pathologic changes including glomeruli, arteriole and tubulo-interstitial fibrosis (IFTA) were semi-quantitatively scored. Arterioles with a ratio of inner/outer luminal diameter greater than 0.5 without hyalinosis were diagnosed as normal ones. The relationships between estimated glomerular filtration rate (eGFR), urine protein excretion and pathological changes were analyzed. Results: A total of 52 patients were enrolled in the study, including 39 males (75.0%). The age of the patients was (45.0±12.7) years at biopsy. Among them, 50 patients (96.2%) had a history of hypertension with a median duration of 66 (24, 138) months. Forty-one patients (78.9%) were overweight or obese. The median urinary protein excretion was 0.75 (0.27, 1.32) g/d with 3 cases over 3 g/d. Fifteen patients (28.8%) presented with microhematuria and twenty-seven patients (51.9%) with eGFR lower than 60 ml·min^-1·(1.73 m²)^-1, respectively. The ratio of arteriolar inner/outer luminal diameter was 0.43±0.05 and the percentage of normal arterioles was 29.0%±17.0%. There were 21 patients (40.4%) found with arteriole hyalinosis. The ratio of arteriolar inner/outer luminal diameter correlated with the percentage of glomerular lesions (r_s=-0.312, P=0.024), the semiquantitative scale of IFTA (r_s=-0.291, P=0.037) and eGFR (r=0.339, P=0.014), respectively. Hypertension duration and body mass index (BMI) showed a negative correlation with the ratio of arteriolar inner/outer luminal diameter (r_s=-0.303, P=0.029 and r_s=-0.274, P=0.050, respectively) and a positive correlation with serum complement 3 level (r_s=0.358, P=0.020 and r_s=0.432, P=0.004, respectively). Conclusions Renal ischemia injury may be found in young and middle-aged patients. The characteristic of clinical features is mild to moderate proteinuria accompanied with a certain degree of eGFR decline, while a small number of patients may have microhematuria and marked proteinuria. The ratio of arteriolar inner/outer luminal diameter has a negative correlation with the percentage of glomerular lesions and the semiquantitative scale of IFTA and a positive correlation with eGFR, respectively. Hypertension and obesity are closely related to vascular lesions.

OBJECTIVES: To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis. METHODS: Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group. RESULTS: The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group. CONCLUSIONS PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.
Autoantibodies ; Glomerulonephritis, Membranous ; Humans ; Immunohistochemistry ; Receptors, Phospholipase A2 ; Thrombospondins

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.
Collagen Type III ; genetics ; Glomerular Mesangium ; Humans ; Kidney Diseases ; Kidney Glomerulus ; Proteinuria