Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Incomplete Miller-Fisher syndrome （MFS） mediated by GT1a antibody often has atypical clinical manifestations and a high misdiagnosis rate. This article reports the diagnosis and treatment of a patient with incomplete MFS mediated by GT1a antibody and discussed clinical manifestations， pathogenesis， and treatment regimens with reference to the relevant literature， so as to improve the understanding of this disease.

AIM:To investigate the synergistic efficacy of travoprost and betahistine mesylate in early open angle glaucoma.METHODS:This study is a prospective, randomized, controlled, open label single center clinical trial that enrolled 82 patients(82 eyes)with early primary open-angle glaucoma from January 2020 to January 2023(eligible eyes were included, and the right eye was selected if both eyes met the inclusion criteria). The patients were randomly divided into a monotherapy group(41 eyes)treated with only travoprost eye drops and a combination therapy group(41 eyes)treated with travoprost eye drops and oral betahistine mesylate according to a 1:1 ratio using a random number table method. Followed-up for 12 mo, the intraocular pressure(IOP), retinal nerve fiber layer(RNFL)thickness, ocular hemodynamics [peak systolic velocity(PSV), end diastolic velocity(EDV), resistance index(RI), pulsatility index(PI)], liver and kidney function, quality of life, and clinical symptom scores before and after treatment were compared between the two groups of patients.RESULTS:Totally 4 patients were unable to complete all follow-up visits due to various factors, including 2 cases in the monotherapy group and 2 cases in the combination therapy group, with a lost rate of follow-up of 5%. The IOP in the combination therapy group was significantly lower than that in the monotherapy group at all time points(all P<0.05). Additionally, the rate of reduction in RNFL thickness was significantly slower in the combination therapy group compared to the monotherapy group(all P<0.05). Hemodynamic parameters revealed that PSV and EDV were significantly higher in the combination therapy group at 12 mo, while RI and PI were significantly lower than those in the monotherapy group(all P<0.05). The quality of life scores and visual analog scale(VAS)scores were also significantly better in the combination therapy group compared to the monotherapy group(all P<0.05). There were no statistically significant differences in liver functions, including alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and kidney functions, including serum creatinine(Scr), blood urea nitrogen(BUN), and uric acid(UA)between the two groups at 6 and 12 mo after treatment, with no serious damage to liver and kidney or other systemic adverse reactions observed in either groups. Furthermore, the incidence of headache in the combination group was lower than that of the monotherapy group(P=0.042), and there were no statistical significance in the incidence of other adverse reactions(all P>0.05).CONCLUSION:The combination therapy of travoprost and betahistine mesylate exhibits significant synergistic effects in patients with early primary open angle glaucoma, offering better IOP control, neuroprotection of the optic nerve, and oxidative stress inhibition. This combination may provide a new clinical reference for comprehensive glaucoma treatment.

Objective To investigate the preliminary clinical effect of closed reduction and cannulated nail internal fixa-tion for femoral neck fracture assisted by robot navigation and positioning system.Methods From July 2019 to January 2020,16 cases of femoral neck fracture(navigation group)were treated with closed reduction and internal fixation guided by robot system,including 7 males and 9 females,aged 25 to 72 years old with an average of(53.61±5.45)years old;Garden classification of fracture:3 cases of type Ⅰ,3 cases of type Ⅱ,8 cases of type Ⅲ,2 cases of type Ⅳ.Non navigation group(control group):20 cases of femoral neck fracture were treated with closed reduction and hollow nail internal fixation,8 males and 12 females,aged 46 to 70 years old with an average of(55.23±4.64)years old;Garden type Ⅰ in 2 cases,type Ⅱ in 4 cases,type Ⅲ in 11 cases,type Ⅳ in 3 cases.The operation time,fluoroscopy times,guide needle drilling times,screw adjustment times,intraoperative bleeding volume and other indicators of two groups were evaluated.Results Both groups were followed up for 12 to 18 months with an average of(15.6±2.8)months.The fractures of both groups were healed without delayed union and nonunion.There was no significant difference in healing time between two groups(P=0.782).There was no significant differ-ence in Harris scores between two groups at the last follow-up(P=0.813).There was no significant difference in operation time between two groups(P＞0.05).There were significant differences between two groups in fluoroscopy times,guide needle drilling times,hollow screw replacement times,and intraoperative bleeding volume(P＜0.05).Conclusion Closed reduction and hollow screw internal fixation assisted by robot navigation system for femoral neck fracture has the advantages of minimally invasive operation,precise screw placement,and reduction of X-ray radiation damage during operation.

Objective:To explore the value of baseline PET/CT parameters for predicting prognosis in patients with double-expression lymphoma (DEL).Methods:The clinical and 18F-FDG PET/CT data of 118 patients (66 males, 52 females; age: 28-85 years) with diffuse large B-cell lymphoma (DLBCL) diagnosed in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University and the First Affiliated Hospital of Nanjing Medical University from June 2015 to September 2022 were retrospectively analyzed. The optimal thresholds for SUV max, total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in predicting overall survival (OS) rate were determined using ROC curve analysis. Univariate and multivariate analyses, along with Kaplan-Meier survival analysis were performed to construct a survival prediction model. The effect of the model was evaluated by the calibration curve for the model, the time-dependent ROC curve analysis and decision curve analysis. Results:As of the last follow-up, 25 patients died, and the OS rate was 78.8%(93/118). The AUC of the ROC curve for TMTV was 0.705, with a corresponding optimal threshold of 230.9 cm 3. In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) score (hazard ratio ( HR)=3.886, 95% CI: 1.455-10.375; P=0.007) and TMTV ( HR=4.649, 95% CI: 1.665-12.979; P=0.003) were identified as independent predictors of OS. The combined model of ECOG PS score and TMTV was superior to ECOG PS score model and TMTV model alone in predicting OS. Conclusion:TMTV, a metabolic indicator, and ECOG PS score, a clinical risk factor, are independent predictors of OS in patients with DEL, and their combination can provide more accurate prognostic predictions.

Objective:To observe the clinical effect of subretinal injection and intravitreal injection of conbercept in the treatment of polypoid choroidal vasculopathy (PCV).Methods:A prospective, randomized double-blind controlled study. From June 2022 to January 2023, 35 patients of 35 eyes with PCV diagnosed at Affiliated Eye Hospital of Nanchang University were included in the study. All patients were first-time recipients of treatment. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA) were performed in all affected eyes. BCVA was performed using an international standard visual acuity chart and converted to logarithmic minimum resolved angle (logMAR) visual acuity for statistical purposes. Enhanced depth imaging with OCT instrument was used to measure the macular retinal thickness (MRT), subfoveal choroidal thickness (SFCT), and pigment epithelium detachment (PED) height. Randomized numerical table method was used to divide the patients into subretinal injection group (group A) and vitreous cavity injection group (Group B), 18 cases with 18 eyes and 17 cases with 17 eyes, respectively. Comparison of age ( t=0.090), disease duration ( t=-0.370), logMAR BCVA ( t=?0.190), MRT ( t=0.860), SFCT ( t=0.247), and PED height ( t=?0.520) between the two groups showed no statistically significant difference ( P>0.05). The eyes of group A were given one subretinal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg), and subsequently administered on demand (PRN); eyes in group B were given intravitreal injection of 10 mg/ml conbercept 0.05 ml (containing conbercept 0.5 mg). The treatment regimen was 3+PRN. Lesions were categorized into active and quiescent according to the results of post-treatment OCT and BCVA. Active lesions were treated with intravitreal injection of conbercept at the same dose as before; stationary lesions were followed up for observation. BCVA and OCT were performed at 1, 2, 3, 6 and 9 months after treatment; ICGA was performed at 3, 6 and 9 months. BCVA, MRT, SFCT, and PED height changes before and after treatment were compared and observed in the affected eyes of the two groups. Independent sample t-test was used to compare between the two groups. Results:With the prolongation of time after treatment, the BCVA of the affected eyes in groups A and B gradually increased, and the MRT, SFCT, and PED height gradually decreased. Compared with group B, at 2, 3, 6, and 9 months after treatment, the BCVA of group A was significantly improved, and the difference was statistically significant ( t=?2.215, ?2.820, ?2.559, ?4.051; P<0.05); at 1, 2, 3, 6, and 9 months after treatment, the MRT of the affected eyes in group A ( t=?2.439, ?3.091, ?3.099, ?3.665, ?5.494), SFCT ( t=?3.370, ?3.058, ?3.268, ?4.220, ?4.121), and PED height ( t=?3.460, ?4.678, ?4.956, ?5.368, ?6.396) were significantly reduced, and the differences were statistically significant ( P<0.05). No complications such as intraocular inflammation, high intraocular pressure, or vitreous hemorrhage occurred in any of the affected eyes during or after treatment. Conclusion:Compared with the intravitreal injection of conbercept, the subretinal injection of conbercept can more effectively reduce the height of MRT, SFCT, PED height, and improve the visual acuity of the affected eyes with PCV.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.