Long non-coding RNA PRR7-AS1 promotes osteosarcoma progression via binding RNF2 to transcriptionally suppress MTUS1.

Introduction: Osteosarcoma is a common bone malignant tumor in adolescents with high mortality and poor prognosis. At present, the progress of osteosarcoma and effective treatment strategies are not clear. This study provides a new potential target for the progression and treatment of osteosarcoma. Methods: The relationship between lncRNA PRR7-AS1 and osteosarcoma was analyzed using the osteosarcoma databases and clinical sample testing. Cell function assays and tumor lung metastasis were employed to study the effects of PRR7-AS1 on tumorigenesis in vivo and in vitro. Potential downstream RNF2 of PRR7-AS1 was identified and explored using RNA pulldown and RIP. The GTRD and KnockTF database were used to predict the downstream target gene, MTUS1, and ChIP-qPCR experiments were used to verify the working mechanismy. Rescue experiments were utilized to confirm the role of MTUS1 in the pathway. Results: Deep mining of osteosarcoma databases combined with clinical sample testing revealed a positive correlation between lncRNA PRR7-AS1 and osteosarcoma progression. Knockdown of PRR7-AS1 inhibited osteosarcoma cell proliferation and metastasis in vitro and in vivo. Mechanistically, RNA pulldown and RIP revealed that PRR7-AS1 may bind RNF2 to play a cancer-promoting role. ChIP-qPCR experiments were utilized to validate the working mechanism of the downstream target gene MTUS1. RNF2 inhibited the transcription of MTUS1 through histone H2A lysine 119 monoubiquitin. Rescue experiments confirmed MTUS1 as a downstream direct target of PRR7-AS1 and RNF2. Discussion: We identified lncRNA PRR7-AS1 as an important oncogene in osteosarcoma progression, indicating that it may be a potential target for diagnosis and prognosis of osteosarcoma.

Gut vascular barrier in the pathogenesis and resolution of Crohn's disease: A novel link from origination to therapy.

The gut vascular barrier (GVB) is the deepest layer of the gut barrier. It mainly comprised gut vascular endothelial cells, enteric glial cells, and pericytes. The GVB facilitates nutrient absorption and blocks bacterial translocation through its size-restricted permeability. Accumulating evidence suggests that dysfunction of this barrier correlates with several clinical pathologies including Crohn's disease (CD). Significant progress has been made to elucidate the mechanism of GVB dysfunction and to confirm the participation of disrupted GVB in the course of CD. However, further analyses are required to pinpoint the specific roles of GVB in CD pathogenesis. Many preclinical models and clinical trials have demonstrated that various agents are effective in protecting the GVB integrity and thus providing a potential CD treatment strategy. Through this review, we established a systemic understanding of the role of GVB in CD pathogenesis and provided novel insights for GVB-targeting strategies in CD treatment.

Macrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice.

Hypercholesterolemia and vascular inflammation are key interconnected contributors to the pathogenesis of atherosclerosis. How hypercholesterolemia initiates vascular inflammation is poorly understood. Here we show in male mice that hypercholesterolemia-driven endothelial activation, monocyte recruitment and atherosclerotic lesion formation are promoted by a crosstalk between macrophages and endothelial cells mediated by the cholesterol metabolite 27-hydroxycholesterol (27HC). The pro-atherogenic actions of macrophage-derived 27HC require endothelial estrogen receptor alpha (ERα) and disassociation of the cytoplasmic scaffolding protein septin 11 from ERα, leading to extranuclear ERα- and septin 11-dependent activation of NF-κB. Furthermore, pharmacologic inhibition of cyp27a1, which generates 27HC, affords atheroprotection by reducing endothelial activation and monocyte recruitment. These findings demonstrate cell-to-cell communication by 27HC, and identify a major causal linkage between the hypercholesterolemia and vascular inflammation that partner to promote atherosclerosis. Interventions interrupting this linkage may provide the means to blunt vascular inflammation without impairing host defense to combat the risk of atherosclerotic cardiovascular disease that remains despite lipid-lowering therapies.

Infliximab response associates with radiologic findings in bio-naïve Crohn's disease.

OBJECTIVES: Since a reliable model for predicting infliximab (IFX) benefits in bio-naïve Crohn's disease (CD) is still lacking, we constructed a magnetic resonance enterography (MRE)-based model to predict the risk of loss of response to IFX in bio-naïve patients with CD. METHODS: This retrospective multicenter study enrolled 188 bio-naïve patients with CD who underwent MRE before IFX therapy. Therapeutic outcomes were determined based on clinical symptoms and endoscopic findings within 52 weeks. The areas of bowel wall segmentation were decided by two experienced radiologists in consensus. Texture features were extracted using the least absolute shrinkage and selection operator, and a radiomic model was built using multivariate logistic regression. The model performance was validated by receiver operating characteristic, calibration curve, and decision curve analysis. RESULTS: The area under the curve of radiomic model was 0.88 (95% confidence interval: 0.82-0.95), and the model provided clinical net benefit in identifying the loss of response to IFX and exhibited remarkable robustness among centers, scanners, and disease characteristics. The high-risk patients defined by the radiomic model were more likely to develop IFX nonresponse than low-risk patients (all p < 0.05). CONCLUSIONS: This novel pretreatment MRE-based model could act as an effective tool for the early estimation of loss of response to IFX in bio-naïve patients with CD. KEY POINTS: • Magnetic resonance enterography model guides infliximab therapy in Crohn's disease. • The model presented significant discrimination and provided net clinical benefit. • Model divided patients into low- and high-risk groups for infliximab failure.

[60]Fullerene-Fused Cyclopentanes: Mechanosynthesis and Photovoltaic Application.

The mechanochemical cascade reaction of [60]fullerene with 3-benzylidene succinimides, diethyl 2-benzylidene succinate, or 2-benzylidene succinonitrile in the presence of an inorganic base has been investigated under solvent-free and ball-milling conditions. This protocol provides an expedient method to afford various [60]fullerene-fused cyclopentanes, showing advantages of good substrate scope, short reaction time, and solvent-free and ambient reaction conditions. Furthermore, representative fullerene products have been applied in inverted planar perovskite solar cells as efficient cathode interlayers.

Characteristics of plasma Epstein-Barr virus DNA in children with primary infection / 中华儿科杂志

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Hollow copper sulfide nanoparticles loading deferoxamine for photothermal antibacterial therapy and promoting angiogenesis / 药学学报

Diabetic ulcer is recognized as a chronic nonhealing wound, often associated with bacterial infection and tissue necrosis, which seriously affect patients' health and quality of life. The traditional treatment methods exist some problems, such as bacterial resistance and secondary trauma, so it is urgent to find new methods to meet the requirements of diabetic ulcer treatment. In this study, we prepared a drug delivery system (DFO@CuS nanoparticles) based on hollow copper sulfide (CuS) nanoparticles loaded with deferoxamine (DFO), which realized the synergistic therapy of promoting angiogenesis and photothermal antibacterial. The morphological structure and particle size distribution of DFO@CuS nanoparticles were characterized by transmission electron microscopy and particle size analyzer, respectively. The antibacterial effect of DFO@CuS nanoparticles was evaluated by the plate coating method. The effects of DFO@CuS nanoparticles on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 (cell counting kit-8) assay, cell scratch assay, and tube formation assay. The results showed that DFO@CuS nanoparticles were hollow and spherical in shape with an average particle size of (200.9 ± 8.6) nm. DFO@CuS nanoparticles could effectively inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) under near-infrared (NIR) light irradiation. DFO@CuS nanoparticles showed negligible cytotoxicity and effective acceleration of cell migration and tube formation in a certain concentration range. In conclusion, the prepared DFO@CuS nanoparticles exhibit good photothermal antibacterial properties and pro-angiogenic effects, providing a basis for their application in the treatment of diabetic ulcer.

Dl-3-N-butylphthalide alleviates renal ischemia-reperfusion injury by down-regulating NF-κB signaling pathway and inhibiting cell pyroptosis in rat models / 器官移植

Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.

Pathogenesis and surgical outcomes of different types of myopic traction maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P&#x003C;0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P&#x003C;0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P&#x003C;0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P&#x003C;0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P&#x003C;0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.

Epo-IGF1R cross talk expands stress-specific progenitors in regenerative erythropoiesis and myeloproliferative neoplasm.

We found that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with colony-forming unit-erythroid (CFU-E) activity (stress CFU-E [sCFU-E]) is expanded markedly to restore the erythron. sCFU-E cells are targets of erythropoietin (Epo), and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2- and STAT5-dependent expression of IRS2, thus engaging the progrowth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R and IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR-lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant JAK2(V617F) in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In samples from patients with myeloproliferative neoplasm, the number of sCFU-E-like cells increases, and inhibition of IGR1R and IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identified a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.

Secondary Indicators for an Evaluation and Guidance System for Quality of Care in Inflammatory Bowel Disease Centers: A Critical Review of the Inflammatory Bowel Disease Quality of Care Center.

The number of patients with inflammatory bowel disease (IBD) has increased remarkably in recent years. However, the level of health care for IBD patients varies greatly among regions of China. Standardization of health care for IBD patients is essential to improve quality of care (QoC). The mission of the IBD Quality Care Evaluation Center (IBDQCC) is to establish indicators for QoC. Since 2017, the IBDQCC has developed structure, process, and outcome indicators with the steering committee of IBD specialists and methodologists; 28 core and 13 secondary IBD QoC indicators were selected using a Delphi method. Applications for certification of IBD quality care units were made voluntarily and preliminarily screened through the IBDQCC committee. Regional units had to meet all core indicators, and units of excellence were required to meet all core indicators together with an additional 50% of secondary indicators. As of 2019 and 2020, 69 IBD units (all from tertiary referral hospitals) have been certified as regional IBD units in China. The certification of excellence of the IBD units is currently undergoing auditing. The awareness of and appreciation for QoC in IBD is increasing in China, especially through the quality control evaluation program initiated by the IBDQCC, with a higher number of IBD units applying for the next round of certification. Although secondary indicators seem to play relatively minor roles in QoC, they suggest additional requirements for high-level centers.

Secondary indicators for an evaluation and guidance system for quality of care promote homogenization of inflammatory bowel disease management for high-level centers.

Effect of plastic and aesthetic surgery on complex facial injuries in children / 中华医学美学美容杂志

Objective:To analyze the anatomical distribution of complex facial injuries (woun-ds ≥8 cm in length and involving two or more anatomical areas) in children, and to explore the effect of plastic and aesthetic surgery.Methods:A total of 157 children with complex facial injury were admitted to the Plastic Surgery Department of Hangzhou Plastic Surgery Hospital from January 2019 to June 2021, including 94 males and 63 females, aged from 2 to 18 years, with an average age of 6.2 years. The wound length was 8-20 cm, with an average length of 10.3 cm. Plastic surgery techniques were used to design different primary repair schemes according to specific wound conditions, and early postoperative scar prevention and treatment were carried out.Results:In 157 cases, 331 anatomical areas were involved, most of which were buccal (75 sites). The injury caused by sharp instruments (glass, ceramic tile, cutting tools, etc.) ranked the first place with 78 cases. All patients were followed up for more than 3 months, and the results showed 146 cases of primary healing, 11 cases of delayed healing, 8 cases of scar hyperplasia, 149 cases of good morphological and functional recovery.Conclusions:The advantages of using plastic and cosmetic surgery techniques to treat complex facial injuries lie in the emphasis on anatomical and functional reduction and tension-reducing suture, combined with a variety of postoperative scar prevention and treatment measures, and the results are satisfactory.

Efficacy and prognostic factors of Ranibizumab in the treatment of macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the therapeutic efficacy of intravitreal injections of ranibizumab for macular edema secondary to retinal vein occlusion(RVO)and the prognostic factors for this disorder.METHODS:A retrospective case study. There were 61 patients(61 eyes)with macular edema secondary to RVO who treated in our hospital from April 2020 to February 2021, including 30 cases(30 eyes)of branch retinal vein occlusion(BRVO)patients and 31 cases(31 eyes)of central retinal vein occlusion(CRVO)patients. All patients received 3 times of intravitreal injections of ranibizumab(0.5mg), and some eyes underwent retinal laser therapy. The patients were followed up for 3mo after treatment(the first intravitreal injection)to observe the visual acuity, intraocular pressure, central retinal thickness(CRT)and record the occurrence of ocular and systemic complications.RESULTS: The visual acuity of the included patients after treatment was significantly improved compared with that before treatment, and the CRT was significantly decreased compared with that before treatment(P&#x003C;0.01), and after 3 times of intravitreal injections, the visual acuity of BRVO and CRVO patients with pre-treatment visual acuity≤1(LogMAR)was better than that of the patients with pre-treatment visual acuity&#x003E;1(P&#x003C;0.01), but there was no difference in CRT(all P &#x003E;0.05). Among BRVO and CRVO patients, 12 and 8 eyes received retinal laser treatment during 3 times of intravitreal injections, respectively. The difference in visual acuity and CRT among the eyes treated with laser and those that were untreated was not significant(P&#x003E;0.05). No ocular and systemic serious complications emerged during follow-up.CONCLUSIONS: Ranibizumab has high efficacy and safety in the treatment of macular edema secondary to RVO, while visual acuity at baseline may help predict the prognosis.

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia

Background/Aims@#The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. @*Methods@#A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. @*Results@#In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. @*Conclusions@#The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Research progress of NF-κB signaling pathway in kidney ischemia-reperfusion injury / 器官移植

Kidney ischemia-reperfusion injury (IRI) is the major cause of poor prognosis after kidney transplantation and partial nephrectomy. Besides, it is also a critical pathophysiological process of acute kidney injury. Consequently, the prevention and treatment of kidney IRI are of significance to improve clinical prognosis of recipients undergoing kidney transplantation. However, the mechanism underlying IRI is complex, and the exact mechanism remains elusive. Inflammation, as one of the main pathogenesis of IRI, plays a significant role in IRI-induced kidney injury. Nuclear factor (NF)-κB, as a rapid response transcription factor, has been proven to be involved in the regulation of inflammation during kidney IRI. Therefore, in this article, the structure of NF-κB, the activation pattern of NF-κB signaling pathway, the regulatory mechanisms of NF-κB upstream and downstream signaling pathways in kidney IRI were reviewed, and the role of NF-κB signaling pathway in kidney IRI was investigated, aiming to provide novel clinical ideas for the prevention and treatment of kidney IRI.

Dexmedetomidine attenuates neuroinflammation by inhibiting NF-κB nuclear translocation in rats with traumatic brain injury / 中华急诊医学杂志

Objective:To explore the mechanism of dexmedetomidine (DEX) regulating microglial (MG) polarization and neuroinflammation after traumatic brain injury (TBI) in rats.Methods:Forty-two adult male SD rats were randomly (random number) divided into the sham group, TBI group, TBI+DEX group (further divided into 1 d, 3 d and 7 d subgroups), TBI+NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC) group and TBI+DEX+PDTC group, with 6 animals in each group. The rat TBI model was established according to the modified Feeney free fall method. PDTC was intraperitoneally injected 1 h after modeling with a dose of 100 mg/kg, and DEX was intraperitoneally injected 2 h after modeling with a dose of 100 μg/kg. Modified neurological severity score (mNSS) was used to evaluate rat neurological function, ELISA was used to detect serum inflammatory factors, and rats’ damaged cortex was collected to detect the phenotype markers of MG and protein expressions of MyD88 and NF-κB p65, and immunofluorescence staining was used to observe the expression and nuclear entry of NF-κB p65 in MG in injured cortex. One-way and two-way ANOVA were used to compare the measurement data among multiple groups.Results:Compared with the sham group, the mNSS score was significantly higher in the TBI group, and DEX treatment significantly decreased the mNSS score of TBI rats ( P<0.05). ELISA and Western blot results showed that in the TBI group, the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β in serum and M1 phenotype marker (TNF-α, IL-1β) in brain were increased, the expression of anti-inflammatory factor IL-10 in serum and M2 phenotype markers (arginase-1 and IL-10) in brain were decreased ( P<0.05), and DEX downregulated the expression of TNF-α, IL-1β in serum and M1 phenotype markers in brain, while upregulated the level of L-10 in serum and the M2 phenotype marker in brain ( P<0.05). In addition, the expression of MyD88 and the nuclear translocation of NF-κB p65 were inhibited in the DEX group, and this effect could be enhanced by PDTC. Conclusions:DEX modulates MG activation in TBI rats by inhibiting NF-κB nuclear translocation and reduces neuroinflammation.

Integrative analysis of long non-coding RNA and messenger RNA expression in toll-like receptor 4-primed mesenchymal stem cells of ankylosing spondylitis.

BACKGROUND: The precise pathogenesis of ankylosing spondylitis (AS) is still largely unknown at present. Our previous study found that toll-like receptor 4 (TLR4) downregulated and performed immunoregulatory dysfunction in mesenchymal stem cells from AS patients (AS-MSCs). The aim of this study was to explore the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in TLR4-primed AS-MSCs, and to clarify the potential mechanisms. METHODS: The immunoregulatory effects of MSCs were determined after TLR4 activation. Next, the differentially-expressed (DE) lncRNAs and mRNAs between AS-MSCs and TLR4-primed AS-MSCs [stimulated by lipopolysaccharide (LPS)] were identified via high-throughput sequencing followed by quantitative real-time PCR (qRT-PCR) confirmation. Finally, bioinformatics analyses were performed to identify the critical biological functions, signaling pathways, and associated functional networks involved in the TLR4-primed immunoregulatory function of AS-MSCs. RESULTS: A total of 147 DE lncRNAs and 698 DE mRNAs were identified between TLR4-primed AS-MSCs and unstimulated AS-MSCs. Of these, 107 lncRNAs were upregulated and 40 were downregulated (fold change ≥2, P<0.05), while 504 mRNAs were upregulated and 194 were downregulated (fold change ≥2, P<0.05). Five lncRNAs and five mRNAs with the largest fold changes were respectively verified by qRT-PCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the DE mRNAs and lncRNAs were highly associated with the inflammatory response, such as NOD-like receptor (NLR) signaling pathway, the TNF signaling pathway and the NF-κB signaling pathway. Cis-regulation prediction revealed eight novel lncRNAs, while trans-regulation prediction revealed 15 lncRNAs, respectively. Eight core pairs of lncRNA and target mRNA in the lncRNA-transcription factor (TF)-mRNA network were as follows: PACERR-PTGS2, LOC105378085-SOD2, LOC107986655-HIVEP2, MICB-DT-MICB, LOC105373925-SP140L, LOC107984251-IFIT5, LOC112268267-GBP2, and LOC101926887-IFIT3, respectively. CONCLUSIONS: TLR4 activation in AS can enhance the immunoregulatory ability of MSCs. Eight core pairs of lncRNA and target mRNA were observed in TLR4-primed AS-MSCs, which could contribute to understanding the potential mechanism of AS-MSC immunoregulatory dysfunction.