Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

A prediction model for sulcus-to-sulcus diameter in myopic eyes: a 1466-sample retrospective study.

BACKGROUND: To establish and verify the accuracy and reliability of a sulcus-to-sulcus diameter (STS) prediction model. METHODS: In this retrospective study, the prediction formula was established with the data from 1466 eyes from 733 subjects from July 2020 to April 2021 and verified with the data from 278 eyes from 139 subjects between May 2021 and June 2021. Each subject was measured with a Pentacam, IOLMaster 700, OPD-Scan III, and ultrasound biomicroscope. The prediction formulas were established with multiple linear regression, and intergroup correlation coefficients (ICCs) and Bland-Altman tests were used to assess the agreement between the predicted and actual STS (actual STS was measured by UBM). RESULTS: The explanatory variables relevant to the horizontal STS (STSH) were the Pentacam white-to-white diameter (WTWP; standardized partial regression coefficient [ß] = 0.330; p < 0.001), the flat K value (ß = -0.211; p < 0.001), and the anterior corneal diameter (ACD) (ß = 0.178; p < 0.001). The corresponding multiple regression equation was : STSH (mm) = 8.061 + 0.510 × WTWP - 0.090 × Flat K value + 0.430 × ACD. The explanatory variables relevant to the vertical STS (STSV) were the WTWP (ß = 0.435; p < 0.001), the steep K value (ß = -0.271; p < 0.001), and the ACD (ß = 0.187; p < 0.001). The corresponding multiple regression equation was : STSV (mm) = 8.540 + 0.492 × WTWP - 0.075 × Steep K value + 0.329 × ACD. The bias of the predicted to the actual STSH was - 0.021, with 95% limits of agreement (95% LoA) from - 0.499 to 0.457. The bias of the predicted to the actual STSV was 0.057, with 95% LoA from - 0.462 to 0.575. The ICC was 0.883 between the predicted and actual STSH and 0.859 between the predicted and actual STSV. CONCLUSIONS: The Pentacam-measured WTW, the K value and the ACD are important for predicting the STS diameter. The prediction model has good accuracy and reliability. TRIAL REGISTRATION: Not applicable.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Short-term changes in and preoperative factors affecting vaulting after posterior chamber phakic Implantable Collamer Lens implantation.

BACKGROUND: To describe the very early vault changes in the first month after Implantable Collamer Lens (ICL) implantation and to evaluate the effect of preoperative biometric factors on vault. METHODS: Eighty-three eyes from eighty-three subjects with complete data who met follow-up requirements were recruited in this retrospective study between May 2019 and March 2020. We quantitatively assessed the postoperative vault at 2 h, 1 day, 1 week, and 1 month following implantation. Associations between the postoperative vault and age, ICL size, spherical equivalent (SE), axial length (AL), central corneal thickness (CCT), flat keratometry (K), steep K, mean K, anterior chamber depth (ACD), crystalline lens thickness (LT), white-to-white (WTW) diameter obtained by three devices, horizontal and vertical sulcus-to-sulcus (STS) diameter, bright and dark pupil sizes (BPS and DPS) and DPS-BPS were investigated using Spearman's correlation analysis and stepwise multiple regression analysis. RESULTS: The mean vault values at 2 h, 1 day, 1 week, and 1 month after ICL implantation were 672.05 ± 30.72, 389.15 ± 28.33, 517.23 ± 30.76 and 530.12 ± 30.22 µm, respectively. Significant differences were found in the vault values at 2 h, 1 day and 1 week after the operation. The ICL size (ß = 0.942; p < 0.001), followed by horizontal STS (ß = -0.517; p < 0.001), crystalline LT (ß = -0.376; p < 0.001) and vertical STS (ß = -0.257; p = 0.017), significantly influenced the vault at 1 month after the operation. The multiple regression equation was expressed as follows: central vault (µm) = -1369.05 + 657.121 × ICL size- 287.408 × horizontal STS - 432.497 × crystalline LT - 137.33 × vertical STS (adjusted R2 = 0.643). CONCLUSIONS: After ICL implantation, the vault decreased and then increased, but it did not return to the vault value 2 h after surgery. The ICL size, horizontal and vertical STS and crystalline LT are key factors for predicting postoperative vaulting.

Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis.

Early diagnosis of liver fibrosis is critical for early intervention and prognosis of various chronic liver diseases. Conventional repeated histological assessment is impractical due to the associated invasiveness. In the current study, we evaluated circulating miR-185 as a potential biomarker to predict initiation and progression of liver fibrosis. We found that miR-185 was significantly up-regulated in blood specimens from patients with HBV-liver fibrosis and rats with liver fibrosis, the miR-185 levels were correlated with liver fibrosis progression, but not with the different viral loads in HBV-infected patients. miR-185 was observed in collagen deposition regions during advanced liver fibrosis. We found that differences in miR-185 levels facilitated the discrimination between early-staged or advanced-staged liver fibrosis and the healthy controls with high specificity, sensitivity, and likelihood ratio using receiver-operator characteristic analysis. miR-185 targeted SREBF1, and increased expression of COL1A1 and a-SMA genes that are hallmarks of liver fibrosis. Our data supported that circulating miR-185 levels could be used as potential biomarkers for the early diagnosis of liver fibrosis.

[Optical characteristics of colored dissolved organic material (CDOM) in Yangtze Estuary].

Absorption property of colored dissolved organic material (CDOM) is one of the most important contents to remote sensing of ocean color in estuarine and coastal areas. In this study, the optical properties and mixing behavior of CDOM in surface water of Yangtze Estuary were discussed according to the two surveys in August of 2008 and May of 2009. Based on the research, the absorption coefficient and spectral slope were discussed. It was found that in summer of 2008 CDOM absorption coefficients at 440 nm [a(g) (440)], ranged from 0.20 m(-1) to 0.73 m(-1), while the coefficients in 2009 varied between 0.20 m(-1) and 0.77 m(-1). Statistics showed that the power function model fitted the best in the regression analysis of CDOM absorption spectral. The spectral slopes (S(g2)) of CDOM calculated by the power function model ranged from 5.10 to 7.90 in Summer of 2008 and from 2.95 to 6.11 in Spring of 2009. The highest absorption coefficients of two cruises appeared both in the south passage of the Yangtze Estuary. The absorption coefficient in surfer water was observed varied tremendously in the estuary and the offshore area. And the main reason is affected by the turbidity maximum zone. It is observed that the absorption coefficients of CDOM tended to a homogeneous distribution whilst the layers of water mixed tempestuously, but otherwise it always showed a conservative mixing behavior. Because of the frequent mixture, there is not assured correlativity between S(g2) and a(g) (440). In the offshore area of Yangtze Estuary, the effecting of local production cannot be negligent, which differed from the estuary area. Yet when the hydrological environment was relatively stable, the negative relationship between them was very clear. In conclusion, the optical properties and mixing behavior of CDOM had showed tremendous different characteristics from inside the estuary to outside the estuary because of the influence of complex physical, chemical and hydrology conditions.