Central serous chorioretinopathy(CSC), the first described pachychoroid disease, is characterized by visual distortions and loss of vision, which are commonly seen in middle-aged male. Research has demonstrated that ocular blood flow in CSC is in a state of overload, characterized by the dilation of vortex vein ampullae and choroidal vasculature. The obstruction of venous outflow is linked to scleral thickness, while the choriocapillaris exhibits perfusion deficits due to compression from the engorged vascular layer. Over time, vascular remodeling occurs, with venous anastomoses forming to create alternative drainage pathways and mitigate blood stasis. These abnormalities in vortex vein dynamics and choroidal circulation play a critical role in elucidating the underlying pathogenesis and clinical manifestations of CSC. This review highlights the alterations in vortex vein and choroidal vasculature in CSC, hoping to understand how the changes of blood flow affect the course of CSC and their correlation with treatment response. By evaluating blood flow dynamics, we aim to determine the disease stage more accurately, optimize therapeutic strategies, and ultimately enhance patient outcomes.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To explore the effect of bismuth containing triple therapy on serum gastrin (Gas), transforming growth factor-α (TGF-α), and high-sensitivity C-reactive protein (hs-CRP) levels in children with Helicobacter pylori (Hp) positive peptic ulcers.Methods:A total of 96 children with Hp positive peptic ulcers admitted to the Second Hospital of Jiaxing from January 2020 to December 2021 were selected as the study subjects. They were randomly divided into two groups using the remainder of a random number table. The control group (48 cases) received treatment with omeprazole, clarithromycin, and amoxicillin, while the observation group (48 cases) received treatment with bismuth containing triple therapy (amoxicillin+ metronidazole+ bismuth potassium citrate). After 10 days of treatment, the clinical efficacy of the two groups was evaluated The improvement time of clinical symptoms, Hp conversion rate, serum indicators (Gas, TGF-α, hs-CRP) before and after treatment, and incidence of adverse reactions were observed.Results:The total effective rate and Hp conversion rate of the observation group were significantly higher than those of the control group [95.83%(46/48) vs 81.25%(39/48), 97.92%(47/48) vs 83.33%(40/48), P<0.05]. The improvement time of upper abdominal pain, heartburn, and acid reflux symptoms was significantly shorter than that of the control group (all P<0.05). After 10 days of treatment, the serum Gas and hs-CRP levels in both groups significantly decreased compared to before treatment (all P<0.05), and the observation group was lower than the control group after treatment ( P<0.05); The levels of TGF-α in both groups increased compared to before treatment (all P<0.05), and the observation group was higher than the control group after treatment ( P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups [4.17%(2/48) vs 2.08%(1/48), P>0.05]. Conclusions:The triple therapy with bismuth containing agents has a better therapeutic effect on children with Hp positive peptic ulcers, and can promote ulcer mucosal repair by improving inflammatory response, with good safety.

Objective To investigate the mechanism of fibroblast growth factor(FGF)21 in liver lipid deposition.Methods HepG2 cells were divided into control group and induction group.Fatty liver cell model was constructed using oleic acid and palmitic acid in induction group.Lipid deposition under the microscope was observed between two groups by oil red O staining,and the protein expression of FGF21 and glutathione peroxidase 4(GPX4)in two groups were detected.FGF21 lentivirus-infected fatty liver cells were used as interference group,and scramble lentivirus-infected fatty liver cells were used as non-interference group.The expression level of FGF21 mRNA,lipid deposition and expression level of GPX4 protein were compared between two groups.Results Compared with control group,induction group had significant lipid deposition,significantly increased expression level of FGF21 protein,and significantly decreased expression level of GPX4 protein(P＜0.05).After the interference of FGF21 lentivirus,expression level of FGF21 mRNA was significantly decreased,lipid droplets were decreased,lipid deposition was significantly improved,and GPX4 protein expression level was significantly increased in interference group(P＜0.05).Conclusion FGF21 may promote liver lipid formation by inhibiting lipid peroxidation.

Objective:To investigate the regulatory effect of vitamin D on the HMGB1/RAGE pathway and adipokine levels in a mouse model of obesity and asthma.Methods:This study was conducted at the Experimental Center of the Second Affiliated Hospital of Jiaxing University and the laboratory of Jiaxing University from February to September 2023. Thirty mice were marked with digital ear numbers and were randomly divided into five groups, with six mice in each group: Group Ⅰ (normal control group), Group Ⅱ (asthma group), Group Ⅲ (obesity and asthma group), Group Ⅳ (asthma + vitamin D group), and Group V (obesity and asthma + vitamin D group). An obesity mouse model was induced using a high-fat diet, while an asthma mouse model was induced through sensitization via intraperitoneal injection of ovalbumin and aerosol inhalation. The vitamin D intervention consisted of continuous intragastric administration of vitamin D (1 mL/d) for 2 weeks. Blood levels of interleukin-4, interleukin-6, interleukin-10, adiponectin, and leptin were determined using the enzyme-linked immunosorbent assay method. The expression of genes encoding high mobility group protein B1 (HMGB1) and the receptor for advanced glycation end products (RAGE) was detected using a quantitative reverse transcription polymerase chain reaction. All the obtained results were statistically analyzed using SPSS software.Results:The white blood cell count in bronchoalveolar lavage fluid (BALF) of Group Ⅱ was (1.34 ± 0.48) × 10 5/L, which was significantly lower than (4.07 ± 0.14) × 10 5/L in Group Ⅳ ( t = -18.28, P < 0.001). The white blood cell count in BALF in Group Ⅲ was (9.61 ± 0.91) × 10 5/L, which was significantly higher than (4.89 ± 0.38) × 10 5/L in Group V ( t = 11.75, P < 0.001). The percentage of eosinophils in BALF of Group II was (28.75 ± 1.94)%, which was significantly higher than (11.51 ± 1.99)% in Group Ⅳ ( t = 15.20, P < 0.001). The percentage of eosinophils in BALF of Group V was (12.50 ± 1.42)%, which was significantly lower than (29.80 ± 1.96)% in Group Ⅲ ( t = 17.74, P < 0.001). The ELISA results demonstrated that serum levels of interleukin-4, interleukin-6, interleukin-17, interleukin-1β, immunoglobulin E, and tumor necrosis factor-α in Group V were significantly lower than those in Group Ⅲ ( t = 15.24, 9.65, 2.26, 5.83, 10.86, 2.50, all P < 0.001). The serum level of interleukin-10 in Group Ⅲ was (4.97 ± 0.25) pg/mL, which was significantly lower than (8.84 ± 0.64) pg/mL in Group V ( t = -13.89, P < 0.001). The serum level of adiponectin in Group V was (1.95 ± 0.85) mg/L, which was significantly higher than (1.15 ± 0.13) mg/L in Group Ⅲ ( t = -12.67, P < 0.001). The HMGB1 expression level in lung tissue of Group Ⅳ was 1.42 ± 0.09, which was significantly lower than 1.91 ± 0.16 in Group Ⅱ ( t = 6.55, P < 0.001). The expression level of RAGE mRNA in lung tissue in Group Ⅳ was 1.35 ± 0.11, which was significantly lower than 1.55 ± 0.152 in Group Ⅱ ( t = 4.19, P < 0.05). The expression level of HMGB1 in lung tissue in Group V was 1.51 ± 0.10, which was significantly lower than 2.44 ± 0.10 in Group Ⅲ ( t = 1.02, P < 0.001). Conclusion:Vitamin D may alleviate lung injury by up-regulating the expression of HMGB1 and RAGE in a mouse model of obesity and asthma. This provides a new concept and method for the treatment and prevention of obesity and asthma.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

Abstract： Objective　To elucidate the antigenic antibody reaction of recombinant expression of non-structural protein 1 (NS1) of Japanese encephalitis (JE) virus with various mosquito-borne flaviviruses, including JE virus, and the antigenic antibody reaction of serum samples of patients infected with JE virus in acute stage. Methods　In this study, Escherichia coli prokaryotic expression vector (pET) system was used to recombinant express Japanese encephalitis virus NS1 gene. Western Blot assay was performed to detect the antibody responses of the recombinantly expressed protein against a variety of mosquito-transmitted flaviviruses, including JE virus, as well as antigen-antibody reactions of serum from patients with acute JE virus infection. Results　The NS1 gene expression product of JE virus (P3 strain) was in the form of an inclusion body, and the denatured and renatured expression product was displayed as a single band in the denatured gel (polyacrylamide gel electrophoresis, PAGE), with a molecular weight of about 45 000. The results of further antigen-antibody analysis showed that the antigen/antibody hybridization reaction of the expression product with polyclonal or monoclonal antibody of JE virus (mosquito isolates, encephalitis isolates) and serum samples of patients with acute JE virus infection could be completely consistent. The recombinant product showed negative antigen/antibody hybridization reactions with mosquito-transmitted flaviviruses, such as dengue virus and yellow fever virus polyclonal antibodies, but positive reactions with polyclonal antibodies to West Nile virus and Murray Valley encephalitis virus. Conclusions　In this study, the recombinant expression of the NS1 protein of JE virus was successfully obtained, and the antigen/antibody reaction between the recombinant protein and samples of patients infected with mosquito-borne flavivirus and JE virus was analyzed. The study results provide important basic data for elucidating the antigen-antibody reaction between the NS1 protein of JE virus and mosquito-borne flavivirus. The recombinant expression protein obtained in this study provides an important material basis for further research on the function of JE virus NS1 protein.

Objective·To investigate the effect of F-box only protein 38(FBXO38)on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA(shRNA)and FBXO38 overexpression plasmids respectively.Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR(qRT-PCR)and Western blotting.The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay.By using The Cancer Genome Atlas(TCGA)database,differentially expressed genes were analyzed in the high and low expression groups of FBXO38.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed to reveal the signaling pathways associated with FBXO38.CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels.qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group,while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group(P＜0.05).Clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells(P＜0.05),while overexpression of FBXO38 inhibited melanoma cell proliferation(P＜0.05).Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma,FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B(PI3K-Akt)pathway activation.Compared with those in the control group,the inhibition rates of P13K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved(P＜0.05),while their inhibition rates of the overexpression group significantly decreased compared with those of control cells(P＜0.05).Western blotting results showed that after knocking down FBXO38,expression levels of PTEN,P21 and P53 proteins decreased,while expression level of MDM2 protein increased.The qRT-PCR results showed a significant decrease in P53 transcription level(P＜0.05)and a significant increase in MDM2 transcription level in FBXO38 knockdown cells(P＜0.05).Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma,and this regulatory effect is related to the PI3K-Akt signaling pathway.

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca²⁺ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca²⁺ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca²⁺ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca²⁺ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca²⁺ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.
Animals ; Astrocytes ; Hippocampus/physiology* ; Humans ; Memory, Short-Term/physiology* ; Mice ; Neurons/physiology* ; Population Dynamics

Objective To explore the scientificity and feasibility of using weighted rank-sum ratio (RSR) method based on diagnosis-related groups ( DRGs) indicators in nursing performance evaluation. Methods Homepage data of medical records were extracted from inpatients discharged in 2017, and " CN-DRGs" burster was used to obtain the DRGs data. Data of medical safety were obtained from the nursing adverse event management system, while data of nursing grading information and medical expenses were obtained from the hospital information system, and the patient satisfaction was obtained in a questionnaire survey. Based on the indicators available, the weighted RSR was applied to evaluate the nursing performance from the 11 dimensions, namely workload, nursing competence, nursing quality, nursing personnel allocation, patient satisfaction, etc. Results The results of the weighted RSR showed that 43, 39, and 6 wards of total 88 wards of the hospital were rated as excellent, medium and poor grades respectively. The results of ANOVA showed that the difference of the 3 grades was significant (F=170. 391, P<0.001). The nursing performance evaluation results were consistent with the actual situation. Conclusions The evaluation of nursing performance with weighted RSR method based on DRGs indicators prove its practical application value, as this method can not only provide data support for nursing personnel allocation, but also provide reference for nursing quality evaluation and supervision.