AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.

Objective:To investigate the effect and molecular mechanism of miR-15a-5p regulation Wnt signaling pathway in PQ-induced pulmonary fibrosis.Methods:The PQ-induced 16HBE cell model was constructed, high-throughput miRNA chip and RT-qPCR were used to screen for miR-15a-5p with significant differences. The experimental groups were as follows: NC group (normal control);no special treatment; PQ group: 50 μmol/L PQ treated cells for 72 h; miR-15a-5p group: 16HBE stable cell lines transfected with miR-15a-5p overexpressing lentivirus; miR-15a-5p+PQ group: Stable cell lines were treated with 50 μmol/L PQ for 72 h. The expression of Wnt pathway-related genes Wnt3α and β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA, epithelial marker genes Occludin and CK18 were detected by RT-qPCR and Western blot. The mice model of PQ-induced pulmonary fibrosis was constructed, and the protein expression and lung tissue injury were detected by Western blot, HE staining and immunohistochemistry. Data were expressed as mean ± standard deviation, and independent sample t-test was used to analyze the data between the two groups. Results:The expressions of Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly up-regulated in cell injury models ( P<0.05), the epithelial cell marker genes Occludin and CK18 significantly down-regulated ( P<0.05), overexpression of miR-15a-5p could inhibit the expression of Wnt3α and alleviated the EMT induced by PQ. In animal models, Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly increased ( P<0.01), the structure of lung tissue was disordered and fibrosis occurred, overexpression of miR-15a-5p inhibited the expression of Wnt3α protein ( P<0.05) and ameliorated lung tissue injury. Conclusions:miR-15a-5p ameliorates PQ-induced lung injury by modulating the Wnt3α/β-catenin signaling pathway, thereby inhibiting the development of pulmonary fibrosis.

Objective:To explore the protective mechanism of Xuebijing injection (referred to as Xuebijing) on sepsis-associated acute respiratory distress syndrome (ARDS).Methods:① Animal experiments: 100 mice were randomly(random number) divided into 4 groups, including sham operation (Sham) group, cecal ligation and puncture (CLP) group, CLP+low-dose Xuebijing (L-XBJ) group, and CLP+high-dose Xuebijing (H-XBJ) group. The survival rate, lung histological changes, lung wet/dry (W/D) ratio, cell count and protein concentration in bronchoalveolar lavage fluids (BALF), inflammatory factors levels in serum, oxidative stress indicators, cell apoptosis, and key proteins of HIF-1α/p38 MAPK/NF-κB signaling pathway were measured. ② Cell experiments: Mouse alveolar macrophages (MH-S) were cultured in vitro and divided into 6 groups, including control (Con) group, lipopolysaccharide (LPS) group, LPS+L-XBJ group, and LPS+H-XBJ group, LPS+H-XBJ+ dimethyloxallyl glycine (DMOG, HIF-1α activator) group, LPS+H-XBJ+ 2-methoxyestradiol (2ME2, HIF-1α inhibitor) group. The effects of Xuebijing on inflammatory factors, oxidative stress, and cell apoptosis and their relationship with HIF-1α/p38 MAPK/NF-κB signaling pathway were detected.Results:Xuebijing increased the survival rate of mice with sepsis-associated ARDS, relieved lung tissue damage [lung injury score: CLP group (8.778±0.588), CLP+L-XBJ group (5.833±0.310), and CLP+H-XBJ group (4.750±0.246)], alleviated lung W/D ratio, and decreased pneumonia cell infiltration and protein exudation (all P<0.05). Additionally, Xuebijing treatment also diminished the expression of inflammatory factors (TNF-α, IL-1β, and IL-6), intracellular reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) formation, superoxide dismutase (SOD) depletion, and cell apoptosis in LPS-induced MH-S cells and CLP-induced sepsis-associated ARDS mice (all P<0.05). Furthermore, mechanistic investigation further clarified the effects of Xuebijing on inflammation, oxidative stress, and cell apoptosis through the HIF-1α/p38 MAPK/NF-κB signaling pathway. Conclusions:Xuebijing can exert anti-inflammatory, anti-oxidative, and anti-apoptotic effects by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway, thereby conferring protection against sepsis-associated ARDS.

Objective To investigate the correlation between serum Angiopoietin-like protein 4(ANGPTL4)and soluble bone marrow cell-like transcription factor-1(sTLT-1)levels and cognitive function and prognosis in elderly patients with vascular dementia(VD).Methods A total of 92 elderly patients with vascular dementia admitted to Hebei Yanda Hospital from June 2020 to June 2022 were selected as the study group.They were divided into mild(n=30),moderate(n=36)and severe groups(n=26)according to the minimum mental state examination(MMSE)score,and 92 patients with healthy physical examination during the same period were selected as the control group.According to the prognosis of patients,the cognitive dysfunction was divided into grade Ⅰ～Ⅱ and grade Ⅲ.ELISA method was used to detect the levels of serum ANGPTL4 and sTLT-1.Pearson and Spearman methods were used to analyze the correlation between serum ANGPTL4 and sTLT-1 and MOCA scores.Logistic regression analysis was used to analyze the influencing factors of the prognostic grade Ⅲ of elderly patients with vascular dementia.The receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of serum ANGPTL4 and sTLT-1 levels in the prognostic grade Ⅲ in elderly patients with vascular dementia.Results The serum ANGPTL4 level(987.57±53.25 pg/ml)in the study group was lower than that in the control group(1 108.35±62.13 pg/ml),and the serum sTLT-1(68.01±5.15 pg/ml)level was higher than that in the control group(50.12±4.57 pg/ml),with significant differences(t=14.158,24.922,all P＜0.05).Serum ANGPTL4 levels and MOCA scores were decreased sequentially in the mild,moderate and severe groups(F=33.495,66.617),while serum sTLT-1 level was increased sequentially(F=66.718),and the differences were statistically significant(all P＜0.05),respective.Pearson analysis showed that serum ANGPTL4 was negatively correlated with sTLT-1(r=-0.621,P＜0.05).Spearman analysis showed serum levels of ANGPTL4 and sTLT-1 were positively and negatively correlated with MoCA scores,respectively(r=0.545,-0.557,all P＜0.05).The serum ANGPTL4 level(953.45±51.16 pg/ml)in the prognostic patients of grade Ⅲ was lower than that of grade Ⅰ～Ⅱ(1 005.76±54.27 pg/ml),and the serum level of sTLT-1(73.14±5.40 pg/ml)was higher than that of grade Ⅰ～Ⅱ(65.28±5.02 pg/ml),with significant differences(t=4.490,6.967,all P＜0.05).Logistic regression analysis showed low expression of ANGPTL4[OR(95％CI):5.089(1.833～14.129)]and high expression of sTLT-1[OR(95％CI):4.258(1.739～10.428)]were risk factors affecting the prognosis of elderly patients with vascular dementia(P＜0.05).According to the ROC curve,the combined prediction of two for the grade Ⅲ prognosis of elderly vascular dementia patients was better than the individual prediction of ANGPTL4 and sTLT-1(Z=2.135,3.268,all P＜0.05).Conclusion Serum ANGPTL4 level was decreased but sTLT-1 level was increased in elderly patients with vascular dementia,and ANGPTL4 and sTLT-1 were closely related to cognitive function and prognosis.

ObjectiveTo explore the clinical efficacy of Huanglian Jiedutang as an adjunctive treatment for acute cerebral infarction complicated with gastric motility disorder. MethodSixty patients with acute cerebral infarction complicated with gastric motility disorder with fire toxin syndrome were randomly divided into a western medicine control group （control group） and a traditional Chinese medicine （TCM） combined treatment group （observation group）， with 30 cases in each group. The control group received basic treatment for cerebral infarction and relevant western medical symptomatic treatment based on the patients' gastrointestinal symptoms. The observation group received Huanglian Jiedutang in addition to the treatment provided to the control group. The treatment course was 7 days. Neurological deficit scores and gastrointestinal dysfunction scores were assessed in both groups before treatment and on the 4^th and 7^th days of treatment. Gastrointestinal electrographic parameters， serum citrulline （CIT）， and motilin （MTL） levels were measured in both groups before treatment and on the 7^th day of treatment. Clinical efficacy was compared between the two groups. ResultCompared with the baseline in both groups， the neurological deficit scores and gastrointestinal dysfunction scores were significantly reduced on the 4th and 7^th days of treatment （P<0.05）. The reductions in these scores were more significant on the 7^th day compared with those on the 4^th day of treatment （P<0.05）. On the 4^th and 7^th days of treatment， the observation group showed a significantly greater reduction in neurological deficit scores and gastrointestinal dysfunction scores compared with the control group （P<0.05）. On the 7th day of treatment， compared with the baseline， both groups showed a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. On the 7th day of treatment， compared with the control group， the observation group had a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. After 7 days of treatment， the total effective rate in the observation group was 90.00% （27/30）， higher than 76.67% （23/30） in the control group， but the difference was not statistically significant. ConclusionAdjunctive treatment with Huanglian Jiedutang can effectively improve the symptoms of neurological function impairment and gastrointestinal dysfunction in patients with acute cerebral infarction complicated with gastric motility disorder， increase gastric antral and gastric body electric wave amplitudes， improve gastric motility disorder， and increase serum CIT and MTL levels， thereby improving the imbalanced secretion function of the gastrointestinal tract.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Objective:To explore abnormal microstructural changes of white matter in patients with white matter lesions(WML) using diffusion tensor imaging(DTI), and to determine the association of such abnormalities of DTI parameters with executive function.Methods:Totally 34 patients with WML were recruited from the department of Neurology, Beijing Tiantan Hospital, Capital Medical University from March 2012 to May 2019.All patients with WML were scored with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA), and assessed with Montreal cognitive assessment (MoCA) and clinical dementia rating(CDR). They were divided into WML-cognitive normal group, WML-vascular cognitive impairment-non dementia group and WML-Dementia group.The Stroop color and word test (SCWT), trail making test-A (TMTA), digit symbol test and verbal fluency test were carried out to evaluate executive function.In addition, the healthy elderly without WML lesions were selected as the control group after they were examined by MRI, and all brains of the subjects went through DTI with Siemens 3.0 T MR.The data were collected and analyzed by voxel based analysis (VBA). The anisotropy and mean diffusion coefficient of DTI in the region of interest (ROI) and other regions in the brain were studied in the four groups, and their correlation with scores of executive function in WML patients was analyzed.Results:(1)In these executive function test, there were significant differences between the patients with cognitive impairment (WML-VAD group, WML-VCIND group) and normal cognition group(WML-CN group, NC group), such as SCWT(B)(65.54±6.24 vs 43.67±0.95, 76.75±2.13 vs 43.67±0. 95, 65.54±6.24 vs 43.66±1.81, 76.75±2.13 vs 43.66±1.81), SCWT(C)(88.58±6.76 vs 61.63±1.31, 96.37±1.47 vs 61 63±1.31, 88.58±6.76 vs 66.31±8.19, 96.37±1.47 vs 66.31±8.19), TMTA(40.47±2.76 vs 30.92±0.47, 44.24±1.43 vs 30.92±0.47, 44.24±1.43 vs 31.99±2.07, 40.47±2.76 vs 31.99±2.07), TMTB(88.66±6.55 vs 80.34±0.61, 96.70±1.72 vs 80.34±0.61, 88.66±6.55 vs 83.10±5.91, 96.70±1.72 vs 83. 10±5.91), Digit Symbol Test(39.25±5.63 vs 47.00±2.55, 31.27±3.93 vs 47.00±2.5, 39.25±5.63 vs 48.86±4.34, 31.27±3.93 vs 48.86±4.34) and Verbal Fluency Test(8.94±1.00 vs 11.71±0.47, 6.64±0.81 vs 11.71±0.47, 8.94±1.00 vs 10.86±0.69, 6.64±0.81 vs 10.86±0.69) scores ( P<0.05); In the patients with cognitive impairment, there were significant differences between WML-VAD group and WML-VCIND group, such as SCWT(B), SCWT(C), TMTA, TMTB, digit symbol test and verbal fluency test scores ( P<0.05); There were significant differences between WML-CN patients and NC group in the scores of SCWT (C), verbal fluency test( P<0.05). (2)FA values in the genu of corpus callosum and the inferior longitudinal fasciculus were negatively correlated with the time of SCWT (B), SCWT (C) and the TMTA( r=-0.436--0.471), but positively correlated with the scores of digit symbol test and verbal fluency test( r=0.428-0.573). MD values in the genu of corpus callosum, the superior/inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus were positively correlated with the time of SCWT (B), SCWT (C) and TMTA( r=0.432~0.609), but negatively correlated with the scores of digit symbol test and verbal fluency test( r=-0.424--0.630, all P<0.003125 after emendation). Conclusion:The executive function of patients with WML-Dementia decreases significantly.The more serious the damage of white matter microstructure, the more serious the damage of executive of function.

Objective:To analyze the characteristic of nerve tracts in different stages of cognitive impairment caused by white matter hypertensities, applying diffusion tensor imaging-peak width of skeletonized mean diffusivity as evaluation indicator.Methods:Demographic characteristics and vascular risk factors of all subjects were recorded.Screened out 50 subjects without WMH and whose MoCA scale was more than or equal 26 points as normal control group.Then, we assessed 85 patients with WMH using the MoCA scale and clinical dementia assessment. Of 85 patients, 45 cases were divided into the normal cognition group, 23 cases were assigned into non-dementia vascular cognitive impairment group, and 17 cases into the vascular dementia group.The diffusion tensor imaging-peak width of skeletonized mean diffusivity marking method was used to compare the integrity of white matter fibers in WMH patients with varying degrees of cognitive impairment and normal control group.Results:The difference of PSMD among the four groups was statistically significant(CN group: 3.558±0.157, VCIND group: 4.128±0.222, VaD group: 5.469±0.000, NC group: 2.612±0.105, F=42.479, P<0.05). PSMD in WMH groups were higher than that in NC group (all P<0.05). There was no significant difference between WMH-VCIND group and WMH-CN group ( P=0.067). The PSMD of WMH-VAD group was higher than that of WMH-CN group and WMH-VCIND group (both P<0.05). Conclusion:PSMD can accurately detect white matter fiber damage caused by WMH.The degree of WMH combined cognitive decline was not completely consistent with the degree of PSMD increase.Compared with the cases with normal WMH cognition, PSMD was not significantly increased when WMH was combined with VCIND, while PSMD was significantly increased when WMH was combined with VaD.DTI-PSMD value as imaging marker can provide objective basis for clinical diagnosis of WMH-VaD.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Objective To investigate the value of the reverse shock index multiplied by GlasgowComa scale score (rSIG) and serum translocator protein 18000 in the prognosis of patients with severe traumatic brain injury. Methods One hundred and fifteen patients with severe traumatic brain injury were divided into the survival group and death group. SPSS 20.0 software was used to compare the vital signs, rSIG and TSPO between the two groups, and the relationship between rSIG and TSPO was analyzed. Receiver operating characteristic (ROC) curve was used to predict the value of rSIG and TSPO and their combination in the prognosis of patients with severe traumatic brain injury. According to the best cut-off value of rSIG and TSPO of ROC curve, patients were divided into the rSIG ≤ 14.8 group and rSIG>14.8 group, and the TSPO ≤ 1.84 ng/mL group and TSPO>1.84 ng/mL group, and the mortality between the groups was compared. Results In 115 patients, rSIG of the survival group was significantly higher than that of the death group, and TSPO was significantly lower than that of the death group [(10.5±4.4) vs. (6.4±4.1), 1.0(0.3,1.9) ng/mL vs.3.4 (2.0, 4.6) ng/mL, P<0.01]. The ability of rSIG combined with TSPO to forecast the mortality of patients with severe traumatic brain injury is not superior to the predictive power of these two indicators alone. The serum TSPO value and 28-day mortality in the rSIG > 4.15 group were significantly higher than those in the rSIG ≤ 4.15 group. The rSIG value of the TSPO ≤ 1.84 ng/mL group was significantly higher than that of the TSPO>1.84 ng/mL group; the 28-day mortality was significantly lower than that in the TSPO>1.84 ng/mL group. The rSIG value was negatively correlated with serum TSPO value (r=-0.611, P<0.01). Conclusions rSIG value and serum TSPO value have good predictive value for the prognosis of patients with severe traumatic brain injury, and can provide certain guiding significance in clinical practice.