Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Pancreatic cancer is a highly malignant digestive tract tumor with hidden symptoms,limited treatment options and rapid progression.With an increasing incidence rate year by year,pancreatic cancer has increasingly become a prominent issue endangering public health,causing a huge social burden.Although there was no significant improvement in survival rates for pancreatic cancer patients in the past two decades,recent progress in epidemiology,basic research and clinical research of pancreatic cancer has accelerated significantly compared to the past.Some findings have already enabled a small proportion of pancreatic cancer patients to achieve better survival.This article provided a review of the significant progress made in research,diagnosis and treatment of pancreatic cancer in 2023.

Objective:To correlate serum Nesfatin-1, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cystatin C (CysC) levels with myocardial enzymes and cardiac function in patients with acute ST-elevation myocardial infarction (STEMI).Methods:This is a case-control study. A total of 100 patients with acute STEMI who received treatment at Lishui People's Hospital from January 2020 to December 2022 were included in the STEMI group. An additional 80 healthy controls who concurrently received physical examinations in the same hospital were included in the control group. Serum levels of Nesfatin-1, NT-proBNP, CysC, creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI) levels were determined in each group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), and left ventricular end-systolic diameter (LVDS) were measured using color Doppler ultrasound. Correlation analysis was performed.Results:Serum Nesfatin-1 level in the STEMI group was (89.96 ± 15.25) ng/L, which was significantly lower than (226.36 ± 37.47) ng/L in the control group ( t = 33.15, P < 0.05). Serum levels of NT-proBNP and CysC in the STEMI group were (1 325.12 ± 378.48) ng/L and (1.37 ± 0.24) mg/L, which were significantly higher than (78.95 ± 13.42) ng/L and (0.79 ± 0.16) mg/L in the control group ( t = -29.42, -18.56, both P < 0.05). Serum CK-MB and cTnI levels in the STEMI group were (46.51 ± 12.14) U/L and (1.13 ± 0.25) U/L, respectively, which were significantly higher than (12.23 ± 4.01) U/L and (0.09 ± 0.02) U/L in the control group ( t = -24.06, -37.09, both P < 0.05). The LVEF in the STEMI group was (37.84 ± 5.45)%, which was significantly lower than (72.41 ± 4.26)% in the control group ( t = 46.49, P < 0.05). The LVDD and LVDS in the STEMI group were (40.92 ± 5.25) mm and (58.98 ± 6.25) mm, which were significantly higher than (19.86 ± 3.36) mm and (34.21 ± 4.38) mm in the control group ( t = -31.13, -30.03, both P < 0.05). Serum Nesfatin-1 level was positively correlated with LVEF ( r = 0.572), but it was negatively correlated with serum CK-MB and cTnI levels, LVDD, and LVDS ( r = -0.498, -0.617, -0.506, -0.534, all P < 0.05). Serum NT-proBNP and CysC levels were negatively correlated with LVEF ( r = -0.653, -0.607), but they were positively correlated with serum CK-MB and cTnI levels, LVDD, and LVDS ( r = 0.582, 0.526, 0.712, 0.565, 0.631, 0.578, 0.659, 0.635, all P < 0.05). Conclusion:Serum Nesfatin-1 levels decrease, while serum NT-proBNP and CysC levels increase in patients with acute STEMI. Serum Nesfatin-1, NT-proBNP, and CysC levels are closely related to myocardial enzymes and cardiac function.

Objective:To explore the reasonable timing of radiotherapy for epidermal growth factor receptor ( EGFR) mutation-positive non-small cell lung cancer patients with brain metastasis in the era of third-generation targeted drugs. Methods:Clinical data of EGFR mutation-positive non-small cell lung cancer patients with brain metastasis who received first-line treatment with third-generation targeted drugs and stereotactic radiotherapy at Shanghai Armed Police Corps Hospital from September 2019 to May 2022 were retrospectively analyzed. According to the timing of radiotherapy before / after targeted drug resistance, all patients were divided into the early and salvage radiotherapy groups. The proportion of brain metastasis, physical fitness, complete response rate, objective response rate, delaying the progression of brain metastasis and overall survival (OS) were compared between two groups. Kaplan-Meier method was used for survival analysis, log-rank test was used for univariate prognostic analysis, and factors with P <0.1 were included in Cox multivariate analysis. Results:A total of 85 patients were included, including 51 (60%) cases receiving early radiotherapy. Patients who participated in early radiotherapy had a higher proportion of symptomatic brain metastasis (82% vs. 56%, P=0.013) and poorer physical fitness (Kanofsky performance score <70: 61% vs. 26%, P=0.002) compared to patients who underwent salvage radiotherapy. Early radiotherapy significantly improved the complete response rate of intracranial lesions (35% vs. 12%, P=0.015) and objective response rate (88% vs. 71%, P=0.041), delayed the progression of brain metastasis (median intracranial progression free survival: 23.0 months vs. 16.0 months, P=0.005; median intracranial secondary progression free survival: 31.0 months vs. 22.0 months, P=0.021), and improved OS (median OS: 44.0 months vs. 35.0 months, P=0.046). In multivariate analysis, diagnosis-specific graded prognostic assessment score <2.5, mutation of EGFR exon 21, and salvage brain radiotherapy were adverse prognostic factors for OS. Conclusion:In the era of third-generation targeted drugs therapy, early involvement of stereotactic radiotherapy in non-small cell lung cancer patients with brain metastasis can bring greater clinical benefits.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Objective:To explore the roles and mechanisms of metformin in the improvement of cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Methods:Total 82 SD male rats (SPF grade) aged 3-4 months were randomly divided into four groups: sham operation control group (Con group, n=15), sham operation with metformin treatment group (Met group, n=20), 2-vessel occlusion group (2VO group, n=22), and 2-vessel occlusion with metformin administration group (2VO+ Met group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries of rats in Con group and Met group were only separated without ligation.After 2VO operation, rats in 2VO+ Met group and Met group were given metformin solution in drinking water at a dose of 100 mg/kg per day for 4 weeks.After 4-week continuous intervention with metformin, Morris water maze was performed to test the spatial cognitive function of the rats, in vivo electrophysiological technology was used to detect the long-term potential of the rats, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of inflammatory factor tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in the hippocampus.The density of dendritic spines of hippocampal neurons was observed by Golgi staining, and the synaptic structure of hippocampal neurons, especially the vesicle density, was observed by transmission electron microscopy.SPSS 16.0 software was used for statistical analysis.Repetitive measurement ANOVA was used for the escape latency data of 7 days repeated learning training in water maze.One-way ANOVA was used for the comparison of other data among multiple groups, and Dunnett's t test was used for further pairwise comparison. Results:Morris water maze results showed that during 7 days of learning training, the time and group interaction for escape latency was not significant in the 4 groups of rats ( F=0.93, P>0.05), but the time main effect ( F=25.90, P<0.05) and group main effect ( F=13.20, P<0.05) were significant.Morris water maze test showed that from the 3rd to 7th day, the escape latencies in 2VO group were significantly longer than those in Con group and 2VO+ Met group(all P<0.05). The short-term memory of rats was detected after 1 day of rest.The results showed that the escape latency in 2VO group was significantly longer than that in Con group and 2VO + Met group( P<0.01). The retention time and crossing times in the platform area of 2VO rats were less than those in Con group and 2VO + Met group ( P<0.01). Electrophysiological results showed that the relative field excitatory postsynaptic potential slope of 2VO group (1.29±0.09) was significantly lower than that in Con group (2.07±0.09) and 2VO + Met group (1.69±0.08)( P<0.01). ELISA results showed that TNF-α level in hippocampal tissue of 2VO group was significantly higher than that in Con group and 2VO+ Met group; IL-1β and IL-6 levels in hippocampal tissue of 2VO group were significantly higher than those in Con group and 2VO + Met group.Density of dendritic spines in hippocampal neurons of 2VO group was significantly lower than that in Con group and 2VO+ Met group.The density and proportion of immature dendritic spines in hippocampal neurons of 2VO group were significantly higher than those in Con group and 2VO + Met group.Synaptic vesicle density of neurons in CA1 area of hippocampus in 2VO group ((230.29±19.44) vescicles/μm 2) was significantly lower than that in the Con group ((414.52±13.17) vescicles/μm 2) and 2VO+ Met group ((313.19±12.42) vescicles/μm 2). Conclusion:Metformin can reduce neuroinflammation of hippocampus with chronic cerebral hypoperfusion and improve synaptic plasticity and cognitive dysfunction.It may have potential application value in the treatment of vascular cognitive dysfunction.

Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.