Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.

Objective:To observe the effect of G protein alpha inhibitory subunit (Gαi) 1 and Gαi3 on signal transduction and angiogenesis induced by Netrin-1 (NTN1) and explore the possible mechanisms.Methods:Twenty male C57BL/6J mice aged 6 to 8 weeks were randomly assigned to a control group and a diabetic group, with 10 mice in each group. Diabete group mice were induced by streptozotocin to establish diabetes model. 12 weeks after modeling, quantitative real-time polymerase chain reaction and Western blot were performed to detect the expression of Ntn1, Gαi1 and Gαi3 in diabetic retinas. Additionally, 35 male C57BL/6J mice aged 2 weeks were randomly stratified into three groups: a control group, an intravitreal injection of NTN1 group (NTN1 group), and a retinal endothelial cell-specific Gαi1/Gαi3 knockdown coupled with intravitreal NTN1 injection group (Gαi1/Gαi3 eKD+NTN1 group), with 15 mice in each of the normal control and NTN1 groups, and 5 mice in the Gαi1/Gαi3 eKD+NTN1 group. Isolectin B4 staining was performed to observe retinal neovascularization. In vitro, human umbilical vein endothelial cells (HUVEC) were divided into four groups: negative control lentiviral transfection group (shC group), negative control lentiviral transfection+NTN1 treatment group (shC+NTN1 group), Gαi1/Gαi3 knockdown group (shGαi1/Gαi3 group), and Gαi1/Gαi3 knockdown+NTN1 treatment group (shGαi1/Gαi3+NTN1 group). The effects of NTN1, Gαi1, and Gαi3 on HUVEC proliferation were assessed using the EdU assay. Transwell assays were conducted to determine the effects on HUVEC migration, and Matrigel assays were used to evaluate the effects on HUVEC tube formation. Protein kinase B (Akt), phosphorylated Akt (p-Akt), ribosomal protein S6 kinase (S6K), phosphorylated S6K (p-S6K), extracellular regulatory protein kinase (Erk1/2), phosphorylated Erk1/2 (p-Erk1/2) protein expression on HUVEC were detected by Western blot.Results:Compared with the control group, the relative expression levels of Ntn1, Gαi1, and Gαi3 mRNA and protein in the diabetic group retina were significantly increased, with statistically significant differences ( t=11.800, 9.298, 10.620, 7.503, 3.432, 8.037; P<0.000 1). Compared with the shC group, the relative expression levels of Gαi1 and Gαi3 mRNA and protein in the shGαi1/Gαi3 group in HUVEC were significantly reduced, showing statistically significant differences ( t=16.310, 16.300, 13.600, 9.068; P<0.000 1). HUVEC proliferation rate, migration number and lumen formation number: compared with shC group, shC+NTN1 group significantly increased, while shGαi1/Gαi3 group and shGαi1/Gαi3+NTN1 group significantly decreased, and the differences were statistically significant ( F=62.750, 49.830, 54.900; P<0.000 1). Compared with the control group, the relative expression levels of Gαi1 and Gαi3 mRNA and protein in retina were significantly decreased in the Gαi1/Gαi3 eKD group, showing statistically significant differences ( t=10.920, 13.460, 9.219, 10.500; P<0.000 1). Retinal neovasculogenesis area: compared with the normal control group, the area of retinal neovasculogenesis increased significantly in the NTN1 group, but decreased significantly in the Gαi1/Gαi3 eKD+NTN1 group, with statistical significance ( F=24.010, P<0.000 1). The protein expression of p-Akt relative to Akt, p-S6K relative to S6K, and p-Erk1/2 relative to Erk1/2: compared with shC group, the protein expression of shC+NTN1 group was significantly increased, while that of shGαi1/Gαi3 group and shGαi1/Gαi3+NTN1 group was significantly decreased, with statistical significance ( F=78.610, 144.400, 77.010; P<0.000 1). Conclusions:NTN1 induces Gαi1/Gαi3 to mediate activation of downstream Akt-mammalian target proteins of rapamycin and Erk1/2, thereby promoting angiogenesis in vivo and in vitro environments. Knocking down Gαi1/Gαi3 significantly reduces the NTN1-induced angiogenesis effect.

Objectives: . The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8. Methods: . Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin–stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm. Results: . Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model’s high clinical applicability. Conclusion . The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.

Objective:To explore the contents and methods of clinical comprehensive evaluation of microecologics, with the example of Bifidobacterium quadruple viable tablet, in order to provide evidence for clinical rational use of microecologics, and microecologics research, development and related decision-making, and to promote rational use of medications. Methods:Based on the research data collected from systematic literature search, health technology assessment methods such as evidence-based medicine and pharmacoeconomics evaluation were used to estimate the safety, efficacy, economics, suitability, accessibility and innovation of Bifidobacterium quadruple viable tablet. Results:In terms of efficacy, Bifidobacterium quadruple viable tablet showed significant therapeutic effects in the treatment of pediatric diarrhea, antibiotic-related diarrhea, diarrhea-predominant irritable bowel syndrome, and secondary diarrhea caused by diseases such as ulcerative colitis, as well as constipation and functional dyspepsia. It can also be used in the treatment of various diseases such as Helicobacter pylori related gastritis, liver cirrhosis, non-alcoholic fatty liver disease. In terms of safety, the incidence of adverse effects of this medication was low, and most were mild to moderate and transient symptoms. In terms of economics, compared with mesalazine alone in the treatment of ulcerative colitis, the incremental cost-effectiveness ratio of combination of Bifidobacterium quadruple viable tablet and mesalazine was 1 743.2. Besides, the daily treatment cost of Bifidobacterium quadruple viable tablet was lower than that of combination of Bifidobacterium triple viable and Bacillus licheniformis (1.87 to 2.80 yuan vs. 2.08 to 5.78 yuan). In terms of innovation, this medication had multiple patents and had been identified as a high-tech product in Zhejiang Province. In terms of suitability, the overall suitability of use and technical characteristics of medication were good. It could be further improved in the aspects of dosage form and system. In terms of accessibility, the price of the medication was stable, affordable and accessible to the general public. Conclusions:Based on the existing evidence, Bifidobacterium quadruple viable tablet presented effective with supported evidences, good safety, accessibility and innovation. The suitability can be further optimized. However, more in-depth and targeted research is needed in terms of economics and innovation in different clinical applications, and there is space for optimization in medication suitability.

Objective:To improve the understanding of indolent mantle cell lymphoma (MCL).Methods:The data of a patient with indolent leukemic MCL in the Second Affiliated Hospital of Nanjing Medical University in May 2013 were collected. The cell morphology was analyzed by using cell smear, the flow cytometry was used to make immunophenotype analysis, the karyotype analysis was performed by usig cytogenetic technique, and polymerase chain reaction (PCR) was used to make the immunoglobulin gene analysis. At the same time, lymph node pathology and immunohistochemistry were also analyzed. The related articles published were reviewed to sum up the characteristics and the treatment of indolent MCL.Results:The male patient aged 60 years was obviously asymptomatic accompanied with slow disease progression, leukemic manifestation and without lymphadenopathy. He received pathological biopsy because of located lymphadenopathy in 2008. Small cell morphology, Kappa light chain immunophenotype, t(11;14) translocation showed after the cytogenetic examination, clonal immune globulin gene rearrangement and low Ki-67 positive index were identified. In situ MCL was diagnosed by retrospective pathology.Conclusions:Indolent MCL is extremely rare. It is typically asymptomatic with none or minimal nodal involvement, indolent disease course, leukemic phase with mild lymphocytosis, Kappa light chain expression, simple karyotype, classical or small cell morphology of tumor cells and the positive index of Ki-67 <10%. In situ MCL can be seen in pathology examination. IgVH gene mutation positive and SOX11 negative expression are notable in indolent MCL. International prognostic index of MCL is probably not appropriate in the prognostic analysis of leukemic indolent MCL. It is emphasized that initial observation and having therapies only after the disease progression can be suited for indolent MCL.

Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Foot-and-Mouth Disease Virus

Background::Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period.Methods::This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared.Results::A total of 124 participants (mean age: 29.5 ± 3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM ( n = 60) and NDP ( n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ± 12.1 mg/dL vs. 89.1 ± 13.4 mg/dL, P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ± 13.4 mg/dL vs. 90.8 ± 15.3 mg/dL, P = 0.009), a longer time spent >140 mg/dL (8.7 ± 9.3% vs. 5.9 ± 10.3%, P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM screening tests. Conclusion::Compared to those with normoglycemia, pregnant women with GDM receiving lifestyle interventions alone had similar intrapartum glucose profiles but higher early postpartum glucose levels and greater glucose variability, providing evidence for modification of the current perinatal glucose monitoring strategy for GDM.Trial Registration::ChiCTR.org.cn, ChiCTR2000030972

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.