Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease

AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o A I L D p a t i e n t s w e r e i n c l u d e d i n t h e experimental group(group E), and 11 healthy subjects were recruited as the control group(group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C(P < 0.01), whereas the percentage of Tregs was lower in the group E patients(P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission(P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment(P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.CONCLUSION A high Th17/Treg ratio appears to predict poor shortterm prognosis in patients with AILD in the active stage.

Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease worldwide.However,to date,there is no ideal therapy for this disease.AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice.METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight.The control group(CON)was allowed ad libitum access to a normal chow diet.The high fat diet group(FAT)and Si-Ni-San group(SNS)were allowed ad libitum access to a high fat diet.The SNS group was intragastrically administered Si-Ni-San freeze-dried powder(5.0 g/kg)once daily,and the CON and FAT groups were intragastrically administered distilled water.After 12 wk,body weight,liver index,visceral fat index,serum alanine aminotransferase(ALT),portal lipopoly-saccharide(LPS),liver tumor necrosis factor(TNF)-αand liver triglycerides were measured.Intestinal microbiota were analyzed using a 16S r DNA sequencing technique.RESULTS Compared with the FAT group,the SNS group exhibited decreased body weight,liver index,visceral fat index,serum ALT,portal LPS,liver TNF-αand liver triglycerides(P<0.05).Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group.In particular,Oscillospira genus was a bacterial biomarker of SNS group samples.CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients

Objective: To evaluate the serum Prostaglandin E2(PGE2) level in Acute-on-chronic liver failure(ACLF) and determine its predicative value for infection.Methods: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic(ROC) curves were used to determine optimal cut-off values to predict infection.Results: Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB(P < 0.000 1). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication(P < 0.000 1). ROC analysis showed that serum PGE2(area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/m L.Conclusions: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.

Microemulsion synthesis of ZnMn2O4/Mn3O4 sub-microrods for Li-ion batteries and their conversion reaction mechanism

The hierarchical ZnMn2O4/Mn3O4 composite sub-microrods were synthesized via a water-in-oil microemulsion method followed by calcination.The ZnMn2O4/Mn3O4 electrode displays an intriguing capacity increasing from 440 to 910 mA·h/g at 500 mA/g during 550 consecutive discharge/charge cycles,and delivers an ultrahigh capacity of 1276 mA·h/g at 100 mA/g,which is much greater than the theoretical capacity of either ZnMn2O4 or Mn3O4 electrode.To investigate the underlying mechanism of this phenomenon,cyclic voltammetry and differential capacity analysis were applied,both of which reveal the emergence and the growth of new reversible redox reactions upon charge/discharge cycling.The new reversible conversions are probably the results of an activation process of the electrode material during the cycling process,leading to the climbing charge storage.However,the capacity exceeding the theoretical value indicates that there are still other factors contributing to the increasing capacity.

Recombinant human thrombopoietin treatment in patients with chronic liver disease-related thrombocytopenia undergoing invasive procedures:A retrospective study

BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.

Sitting and watching the clouds and mountains Liiiang xianglu Health Valley Landscape Design

According to the analysis of waterfront district natural landscape and resources in Lijiang xianglu Health Valley, combined with the human experience of the five senses motion, in this paper, we put forward three functons of proposed, scenery and quiet space, arrange a southbound horse and pedestrian route line categories, andcreate a viewing platform, rest points and landscape landscape boardwalk node to meet the requirement of owners＇ healthy.

Effect of large thickness-reduction on microstructure evolution and tensile properties of Mg-9Al-1Zn alloy processed by hard-plate rolling

The effect of large thickness-reduction on microstructure evolution and tensile properties of Mg-9 Al-1 Zn alloy(AZ91)processed by hard-plate rolling(HPR)was investigated.Increasing rolling reduction from55%to 85%increases the volume fraction and refines average size of fine grains(<3μm,FGs),leading to an optimized bimodal-grained structure consisting of coarse grains(CGs)uniformly embedded in FG regions.The sample with 85%reduction exhibits the highest yield strength of~314 MPa,ultimate tensile strength of~381 MPa and elongation of~11%.The high strength is primarily due to the contribution of grain boundaries(GBs)strengthening by FGs(accounting for~65%of strength),meanwhile the improved ductility originates from the optimized bimodal-grained structure and weakened basal texture that favor a higher ductility.The present findings successfully overcome the trade-off dilemma that the largereduction rolling processing on Mg alloys usually enhances strength at expense of ductility.In addition,the intensified heterogeneous deformation and favorable formation of a bimodal-grained microstructure during large-reduct ion HPR was addressed by tracing micro structure evolution details in grains of intere st via quasi-in-situ electron back scattering diffraction(EBSD).The present study can be instructive for further designing novel Mg alloys by tailoring bimodal-grained structures for superior combination of mechanical properties.

Bone Metabolic Markers in Patients with Obstructive Sleep Apnea Syndrome

Background： Obstructive sleep apnea syndrome （OSAS） is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers. Methods： A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density （BMD） and the serum levels of total procollagen type 1 N-tenninal propeptide （t-P I NP）, N-terminal midfragment ofosteocalcin （N-MID）, [3-C-terminal telopeptide of type 1 collagen （β-CTX）, vitamin D （VD）, and parathyroid hormone （PTH） were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses. Results： No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels oft-P1NP and [3-CTX in the severe OSAS group were significantly higher than those in the obesity group （48.42 ±23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P 〈 0.001 ; 0.53 ± 0.24 ng/ml vs. 0.41 ±0.13 ng/ml, P 0.011, respectively）. The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups （both P 〈 0.001 ）, and decreased as the severity of OSAS increased （P 〈 0.001）. The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups （both P 〈 0.001 ）. The results of correlation analysis indicated that the level of apnea-hypopnea index （AHI） was correlated with the levels oft-P1NP （r = 0.396, P 〈 0.001 ）, VD （r = 0.404, P 〈 0.001 ）, and PTH （r = 0.400, P 〈 0.001 ）, whereas the level of minimum 02 saturation （SaO2min） was correlated with the levels ofVD （r = 0.258, P=0.016） andPTH（r= 0.376, P〈0.001）. Conclusions： The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.

A six-herb Chinese medicine composition ointment as a promising candidate for treatment of hypertrophic scars

Objective:To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition(SCMC) ointment on the rabbit ear hypertrophic scar models.Methods:The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests.The SCMC ointment was prepared through emulsifying method.The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment.Results:Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements.Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading,and took an unobvious but palpable shift from hard to soft texture with the low,middle and high concentration SCMC ointments treatments in vivo.Additionally,on 21 st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group,in a concentration-dependent manner.The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation.Conclusion:The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues.Our research has demonstrated the Chinese medicine composition ointment with good antihypertrophic scar properties that could be used to treat hypertrophic scars.Meanwhile,it provides a theoretical basis for further clinical application.