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.

Primary hepatic cancer is one of the major problems that need to be solved urgently in the field of public health, seriously endangering the life and health of Chinese people. Its treatment mode is multidisciplinary participation and synergy of multiple therapeutic methods. Even though there are many common clinical treatments for liver cancer in China, its therapeutic outcome is still unsatisfactory. yttrium-90 has been applied for more than 20 years, and a large amount of foreign clinical data have been accumulated. Combining the latest literature and clinical practice, the authors describe the clinical application and research progress of yttrium-90 micro-sphere selective internal radiation therapy in primary liver cancer.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Objective To observe the efficacy of dapagliflozin tablets combination with sacubitril/valsartan sodium tablets in the treatment of patients with heart failure(HF)after acute myocardial infarction(AMI)intervention.Methods Patients with HF after AMI intervention were randomly divided into control group and treatment group.The control group was given conventional anti-heart failure therapy+sacubitril/valsartan sodium tablets(50 mg for the first time,then gradually increased to 200 mg each time,twice a day),and the treatment group was additionally treated with dapagliflozin(10 mg every time,once a day)on the basis of the control group,and the course of treatment was 6 months.The two groups were compared in terms of clinical efficacy,cardiac function[left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI),6-minute walking distance(6MWD)],heart failure markers[brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP),troponin(Tn)],and serum related biochemical indicators[soluble human stromelysin-2(ST2),angiotensin 2(AT-Ⅱ),soluble intercellular adhesion molecule-1(sICAM-1)],incidence rates of major adverse cardiovascular events(MACE)during follow-up and adverse drug reactions during treatment.Results Six cases dropped out during treatment,and finally 46 cases were included in control group and treatment group,respectively.After treatment,the effective rates of treatment in treatment group(91.30％)was significantly higher than that in control group(76.09％,P＜0.05).After treatment,the LVEF values in control group and treatment group were(51.38±4.82)％and(54.43±4.63)％;LVRI values were(1.47±0.15)and(1.35±0.17)g·mL-1;6MWD values were(390.53±40.32)and(362.61±38.51)m;the BNP levels were(28.34±2.47)and(26.51±2.16)pmol·L-1;NT-proBNP levels were(262.61±53.18)and(227.68±46.73)ng·L-1;sICAM-1 levels were(84.61±7.14)μg·L-1 and(74.68±7.08)μg·L1,and there were statistical differences between both groups(all P＜0.05).During follow-up,the incidence rate of MACE in treatment group(6.52％)was significantly lower than that in control group(21.74％,P＜0.05).The main adverse drug reactions in the two groups were renal dysfunction,hypotension,urogenital infection and hyperkalemia,but there was no significant difference in the incidence of adverse reactions between treatment group(13.04％)and control group(10.87％,P＞0.05).Conclusion Dapagliflozin tablets combined with sacubitril/valsartan sodium tablets can significantly improve cardiac function and related indicators and reduce the incidence of MACE in patients with HF after AMI intervention.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

Objective:To investigate the safety and short-term efficacy of yttrium-90 [ 90Y] resin microspheres transarterial radioembolization (TARE) for the treatment of initial unresectable malignant hepatic tumor. Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with initial unresectable malignant hepatic tumor who were admitted to The First Affiliated Hospital of Army Medical University from June 2022 to June 2023 were collected. All patients were males, aged (57±4)years. Measurement data with normal distribution were represented as Mean± SD, and comparison before and after treatment within the group was conducted using the paired t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison before and after treatment within the group was conducted using the paired rank sum test. Count data were described as absolute numbers or proportions. Results:(1) Pre-treatment assessment. All 10 patients completed pre-treatment assessment, with 8 cases undergoing once of technetium 99-polymerised protein perfusion test and 2 cases under-going ≥ twice of technetium 99-polymerised protein perfusion test. The ratio of uptake of techne-tium 99-polymerised protein in tumor tissue to normal tissue, the hepatopulmonary shunting ratio and the therapeutic requirement of 90Y resin microspheres in 10 patients were 5.8±1.2, 4.8%±0.8% and (1.10±0.20)GBq, respectively. (2) Treatment strategy of 90Y resin microspheres TARE. Of the 10 patients, cases treated with whole tumor radioembolisation, radioembolisation of the main target lesion+non-target lesion radiofrequency ablation, radioembolisation of the main target lesion+non-target lesion iodine-125 particles implantation, radioembolisation of the liver lobe or liver segment were 6, 2, 1, 1, respectively. During the treatment period, one elderly case did not receive target therapy combined with immunotherapy due to intolerance, and the remaining 9 cases received target therapy combined with immunotherapy. Of the 10 patients, there were 7 cases receiving once of 90Y resin microspheres TARE, and 3 cases receiving twice of 90Y resin microspheres TARE. (3) Follow-up. All 10 patients were followed up for 4.5(range, 3.0-12.0)months. During the follow-up, none of patient had adverse event associated with 90Y resin microspheres TARE. The tumor diameter, alpha-fetoprotein (AFP), abnormal prothrombin, alanine aminotransferase (ALT), aspartate amino-transferase (AST), albumin (Alb), total bilirubin (TBiL), glutamyltransferase (GGT) of the 10 patients were 96(72,135)mm, 26(6,833)μg/L, 290(56,2 997)Au/L, (36±13)IU/L, (41+16)IU/L, (40±4)g/L, (15.3±4.1)μmol/L, (99±68)IU/L before receiving 90Y microspheres TARE. The above indicators of the 10 patients were 63(43,97)mm, 4(3,357)μg/L, 38(25, 142) Au/L, (40±16)IU/L, (51±28)IU/L, (39±4)g/L, (14.4±1.2) μmol/L, (134±93)IU/L after 90 days of receiving 90Y microspheres TARE. There were significant differences in tumor diameter and abnormal prothrombin ( Z=-2.08, -2.24, P<0.05) and there was no significant difference in AFP, ALT, AST, Alb, TBil, GGT ( Z=-1.27, t=0.63, 1.69, 1.73, 0.67, 1.30, P>0.05). During the follow-up period, 5 cases achieved clinical complete response, 4 cases achieved clinical partial remission, and 1 case experienced non-target lesion progression within 30 days after receiving 90Y resin microspheres TARE. The disease remission rate and disease control rate of the 10 patients were 9/10 and 9/10, respectively. None of patient died during follow-up period. Conclusion:90Y resin microspheres TARE for the treatment of initial unresectable malignant hepatic tumor is safe and feasible, and can achieve satisfactory short-term efficacy when combined with other treatment methods.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.