Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective:To compare bowel preparation quality between 2.0 L and 1.5 L polyethylene glycol (PEG) regimens with optimized dietary restrictions.Methods:This study was a randomized controlled trial conducted in three hospitals: the First Affiliated Hospital of Naval Medical University ( n=57), Huadong Hospital Affiliated to Fudan University ( n=30), and General Hospital of Northern Theater Command ( n=30) from May 5th to 30th, 2024. Participants consumed food for special medical purpose one day before examination or therapeutic colonoscopy and were randomized to receive either 2.0 L PEG (group A) or 1.5 L PEG (group B). Outcomes included the completion rate of bowel preparation, the adequate/excellent bowel preparation rate, Boston bowel preparation scale scores, the subject/endoscopist satisfaction, the willingness to repeat the preparation regimen, and incidence of adverse events. Results:A total of 60 subjects in group A and 57 in group B were included. There was no significant difference in baseline characteristics between the two groups ( P>0.05). The adequate bowel preparation rate [81.7% (49/60) VS 64.9% (37/57), χ2=4.21, P=0.040] and endoscopist satisfaction [88.3% (53/60) VS 70.2% (40/57), χ2=5.91, P=0.015] in group A were significantly higher than those in group B. There were no significant differences in bowel preparation completion rates, the excellent bowel preparation rate, the bowel preparation score, subject satisfaction, willingness to repeat the preparation regimen, or incidence of adverse events ( P>0.05). Conclusion:When combined with optimized dietary restrictions, 2.0 L PEG provides superior bowel preparation quality compared with 1.5 L PEG.

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

Objective:To compare bowel preparation quality between 2.0 L and 1.5 L polyethylene glycol (PEG) regimens with optimized dietary restrictions.Methods:This study was a randomized controlled trial conducted in three hospitals: the First Affiliated Hospital of Naval Medical University ( n=57), Huadong Hospital Affiliated to Fudan University ( n=30), and General Hospital of Northern Theater Command ( n=30) from May 5th to 30th, 2024. Participants consumed food for special medical purpose one day before examination or therapeutic colonoscopy and were randomized to receive either 2.0 L PEG (group A) or 1.5 L PEG (group B). Outcomes included the completion rate of bowel preparation, the adequate/excellent bowel preparation rate, Boston bowel preparation scale scores, the subject/endoscopist satisfaction, the willingness to repeat the preparation regimen, and incidence of adverse events. Results:A total of 60 subjects in group A and 57 in group B were included. There was no significant difference in baseline characteristics between the two groups ( P>0.05). The adequate bowel preparation rate [81.7% (49/60) VS 64.9% (37/57), χ2=4.21, P=0.040] and endoscopist satisfaction [88.3% (53/60) VS 70.2% (40/57), χ2=5.91, P=0.015] in group A were significantly higher than those in group B. There were no significant differences in bowel preparation completion rates, the excellent bowel preparation rate, the bowel preparation score, subject satisfaction, willingness to repeat the preparation regimen, or incidence of adverse events ( P>0.05). Conclusion:When combined with optimized dietary restrictions, 2.0 L PEG provides superior bowel preparation quality compared with 1.5 L PEG.

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.

Objective:To prepare a novel 68Ga-labeled bicyclic peptide targeting poliovirus receptor related protein 4 (PVRL4, Nectin-4), and evaluate its feasibility for breast cancer imaging via in vitro and in vivo experiments. Methods:A Biotin-modified bicyclic peptide targeting Nectin-4, Biotin-BMIC, was synthesized, and its targeting properties were preliminarily evaluated by in vitro cell staining experiments. BMIC was modified by 1, 4, 7-triazonane-1, 4-diacetic acid (NODA) and the labeling precursor NODA-BMIC was prepared. A potential PET probe targeting Nectin-4, 68Ga-NODA-BMIC was prepared by one-step labeling strategy. The imaging properties of the probe were investigated by in vivo microPET imaging and in vitro experiments in mice bearing breast tumors. Data were analyzed by independent-sample t test and repeated measures analysis of variance. Results:Fluorescence staining of the cells showed that the fluorescently labeled bicyclic peptide, Biotin-BMIC, was highly aggregated in Nectin-4 positive BT474 breast cancer cells compared to those in Nectin-4 negative MDA-MB-231 cells. The uncorrected yield of 68Ga-NODA-BMIC was (71.5±2.2)% and the radiochemical purity was greater than 95%. The specific activity was greater than 3 GBq/μmol. After incubation 10, 30, 60 and 120 min, higher radioactivity uptakes were found in BT474 breast cancer cells compared to those in MDA-MB-231 breast cancer cells respectively ( F=1 302.00, P<0.001). MicroPET imaging showed that the BT474 xenograft tumors were clearly visible with favorable contrast. A significant statistical difference in uptakes between BT474 and MDA-MB-231 xenograft tumor uptake at 10, 30, 60, and 120 min after probe injection respectively was existed ( F=1 826.00, P<0.001). At 60 min postinjection, the uptake value of BT474 tumors was (5.03±0.14) percentage activity of injection dose per gram of tissue (%ID/g), which was significantly higher than that of MDA-MB-231 tumors ((0.19±0.04) %ID/g; t=79.40, P<0.001). Meanwhile, the tumor-to-muscle ratios in the former were also greater than those in the latter ( F=222.00, P<0.001). At 60 min postinjection, the tumor-to-muscle ratio in the former was significantly higher than that in the latter (24.75±3.10 vs 1.30±0.15; t=14.31, P=0.002). The results were consistent with the immunohistochemistry staining. Conclusions:A novel bicyclic peptide PET probe targeting Nectin-4, 68Ga-NODA-BMIC, is easy to be synthesized and owns satisfactory labeling yield and radiological purity. The imaging performance is good and the target tissues could be visualized. It may play a unique role in the diagnosis and treatment of breast cancer.

OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases