Objective To observe the difference of vascular endothelial growth factor (VEGF) and myeloperoxidase (MPO) between diabetic and non-diabetic patients with maintenance hemodialysis (MHD),and to explore whether it was associated with duration of hemodialysis.Methods A total of 120 patients with MHD were divided into diabetic group (40 cases) and non-diabetic group (80 cases) according to the primary disease.The blood samples from the patients before dialysis were selected to test the serum VEGF and plasma MPO and other indicators.The blood samples from April 2012 to March 2013 were labeled diabetic group 1(40 cases) and non-diabetic group 1 (80 cases).The blood samples from April 2013 to March 2014 were labeled diabetic group 2 (40 cases) and non-diabetic group 2 (80 cases).Results The serum VEGF and plasma MPO levels were (74.63 ± 47.43) ng/L,(300.63 ± 235.37) μ g/L in diabetic group 1,and (63.69 ± 43.23) ng/L,(275.35 ± 216.32) μ g/L in non-diabetic group 1,and there were significant differences between two groups (P ＜ 0.05).The serum VEGF and plasma MPO levels were (83.32 ± 40.38) ng/L,(414.12 ±265.52) μg/L in diabetic group 2,and (70.89 ±39.74) rig/L,(289.45 ±202.85) μg/L in non-diabetic group 2,and there were significant differences between two groups (P ＜ 0.05).The correlation analysis showed that VEGF was positively correlated with MPO in diabetic group 1 and diabetic group 2 (r =0.632 and 0.763,P ＜ 0.05),and VEGF was positively correlated with MPO in non-diabetic group 1 and non-diabetic group 2 (r =0.610 and 0.713,P ＜ 0.05).Conclusions Compared with those in non-diabetic MHD patients,VEGF and MPO levels are significandy higher in diabetic MHD patients.In non-diabetic MHD patients and diabetic MHD patients,VEGF and MPO levels will rise gradually with duration of hemodialysis.The expressions of VEGF and MPO are associated with each other.

Objective To evaluate clinical remission in patients with small bowel Crohn's disease (SBCD) who have received infliximab(IFX) therapy and to evaluate capsule endoscopy combined with ileocolonoscopy for mucosal healing at 14th week of IFX therapy.Methods Clinical data of 23 SBCD patients who received IFX were retrospectively analyzed.Laboratory indices [routine blood tests,C-reactive protein (CRP)and albumin],Crohn's disease activity index (CDAI),Lewis score (LS),Crohn's disease simplified endoscopic score (SES-CD),side effects and complications were compared before IFX treatment and at 14th week of IFX therapy.Results In 23 SBCD patients,both CDAI and CRP levels significantly decreased (P＜0.01) while body mass index (BMI) and albumin levels increased at 14th week (P＜0.05),compared with those before treatment.The clinical remission rate at 14th week was 91.3％ (21/23).There were 8/23 (34.8％)SBCD patients achieving mucosal healing in small bowel,12/21 (57.1％) in terminal ileum and colon,and 7/21 (33.3％) in both small bowel and colon.Twelve patients achieved both clinical remission and biochemical remission at 14th week and all of them achieved mucosal healing in both terminal ileum and colon (SES-CD ≤ 2).However,there were 5 (41.7％) of them still with small bowel inflammation (LS＞ 135).Conclusion IFX plays a role in promoting clinical remission and mucosal healing in SBCD patients.Mucosal healing of CD patients in terminal ileum and other parts of small intestine are not synchronized.For CD patients with small bowel and colon involved,the evaluation of the whole gastrointestinal tract by capsule endoscopy combined with ileocolonoscopy is recommended on condition that they have no intestinal obstruction or severe stricture.

Objective To study the relationship between jejunal-ileum lesions and terminal ileum lesions of patients with isolated small intestinal Crohn disease, and to compare the clinical and endoscopic features of patients having normal terminal ileum with those having abnormal terminal ileum in isolated small intestinal Crohn disease. Methods The data of patients diagnosed as having isolated small intestinal Crohn disease and successively receiving colonoscopy and small bowel capsule endoscopy in Nanfang Hospital of Southern Medical University from January 2008 to October 2015 were retrospectively analyzed. The patients were divided into normal terminal ileum group and abnormal terminal ileum group according to the result of colonoscopy. The clinical and endoscopic features of the two groups were compared. Results The data of 62 patients were collected, and jejunal-ileum lesions were found in all of the patients under small bowel capsule endoscopy. According to the result of colonoscopy, 40 patients ( 64. 5%) were grouped to the abnormal terminal ileum group and 22 patients ( 35. 5%) to the normal group. The patients in the normal terminal ileum group had a shorter disease duration than those of the abnormal group [ 68. 2%( 15/22) VS 12. 5%( 15/40) , P=0. 021] . The sex and age distribution, smoking history, clinical feature, upper gastrointestinal involvement, perianal lesion, disease behavior, Crohn disease activity index, inflammation markers and nutriture between the two groups had no statistical difference ( P>0. 05) . Conclusion The terminal ileum lesions found by colonoscopy cannot predict small bowel lesions for Crohn disease. Small bowel capsule endoscopy is helpful for the detection of small intestinal lesions in Crohn disease. We should pay more attention to evaluating the small bowel lesions when the patients with Crohn disease have a short duration and normal terminal ileum.

Objective To assess the protective effect of rabbit serum paraoxonase-1 (PON-1) on renal injury induced by dichlorvos in rats.Methods Totally 30 healthy S-D rats were randomly divided into 5 groups:control group (group A,n =6),exposure group (group B,n =6),PON-1 pretreatment group (group C,n =6),traditional atropine,pralidoxime treatment group (group D,n =6) and combination therapy group (group E,n =6).The rats of group A were given normal saline in equal volume of dichlorvos injected into abdominal cavity to make a false model of dichlorvos poisoning.In rats of groups B,C,D and E,9 mg/kg dichlorvos was administered.In rats of groups C and E,PON-1 4 500 units/kg was injected into vein of the tails half an hour before dichlorvos administration.After dichlorvos exposure,rats in group D and E were treated with 45 mg/kg iodoprofen and 10 mg/kg atropine by intraperitoneal injection.The activity of blood urea nitrogen (BUN) was assayed with urease.Serum creatinine (Cr) were measured by picric acid colorimetry.Serum Cys-C,KIM-1 and NAG in urine were determined by ELISA.Ultrastructural changes in renal tissues of rats were examined by light microscopy.The differences in laboratory findings between groups were compared.Results The creatinine level in group B was significantly higher than that in other groups (P ＜0.05).The levels of Cys-C,KIM-1 and NAG in group B and group D were significantly higher than those in group A (P ＜ 0.01).But there were no significant differences in above biomarkers among group C,group E and group A.There were no significant differences in above biomarkers between group B and group D.In group B,inflammatory cells infiltrated extensively in renal tissues and,the renal cells were congested and edematous,the lumen was obliterated and the border of the brush disappeared.The tubular structures were not clearly distinct found in group B,but edema and inflammatory cell infiltration with lesser degree were found in group D than those in dichlorvos exposure groups.The clearly distinct structure of the tube without completely occluded lumen in group D,and the most serious lesions were found in distal convoluted tubules.In group C,and group E,there were only mild congestion and edema without significant cell degeneration and necrosis.In group A,the structure of renal tubular epithelium was clearly distinct with brush-shaped margin,and without tubular or necrotic cell debris in the lumen.Conclusion The rabbit serum PON-1 can protect the renal tissue of rats after dichlorvos exposure.

Objective To explore whether the use of purified rabbit serum paraoxonase 1 (PON1) for the treatment of dichlorvos-induced liver injury in rats is superior to traditional method.Methods Thirty male SD rats were randomly divided into the followint 5 groups,with 6 rats in each group:control group (A group),dichlorvos group (B group),traditional treatment group (C group),PON 1 treatment group (D group),combined treatment group (E group).Rats in groups B,C,D and E were adminstered dichlorvos by intraperitoneal injection 9 mg/kg.In group C,atropine 10 mg/kg and iodine solution 45 mg/kg were injected intraperitoneally within 2 min after dichlorvos administration.In group D,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning.In group E,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning,followed by in travenous injection of atropine 10 mg/kg and iodine solution 45 rng/kg within 2 min after poisoning.Rats in A group received normal saline.Blood was collected at different time points to examine the acetyl cholinesterase (AChE)-levels by ELISA method.Liver tissue were collected at 12 hours after model establishment to observe the pathological changes.The expression of 4 hydroxy 2-nonenal (4-HNE) in the liver tissue was detected by immunohistochemistry and Western blotting.Results In group B,AChE levels decreased significantly,liver cells showed severn fatty degeneration,karyopyknosis and other pathological changes,and 4-HNE expression increased.The pathological changes of group D and group E were less obvious than those of group C,and the 4-HNE expression in the group D and group E were significantly different from that in the group C (P＜ 0.05).Conclusion PON1 plays a protective role in dichlorvos-induced liver injury in rats,and this protection is better than that offered by traditional treatment.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Objective·To explore the immune-related characteristics of non-small cell lung cancer(NSCLC),discover potential tumor markers in V-J genes,and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor(TCR)repertoire analysis workflow.The upstream analysis included steps such as raw data processing,quality control,filtering,TCR sequence identification,and extraction.The downstream analysis included repertoire clone distribution,clone typing,V-J gene sharing,CDR3 distribution characteristics,and clone tracking.The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chaol index.Clone typing was performed based on the number of clone amplifications to explore differences among different types.The degree of V-J gene segment sharing was analyzed,and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma.Finally,analysis of the distribution characteristics of V genes and high-frequency clone type CDR3,and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis,aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues,as well as among different ages and genders.② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing,and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis.③ In the analysis of high-frequency clone type clone tracking,highly expressed or newly expressed high-frequency clone types were observed in NSCLC,suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens.④ It was found that the expression frequency of TRBJ2-5 gene,originally low-expressed,significantly increased,indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers.

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.