OBJECTIVE: To explore the protective effects and underlying mechanisms of H ₂S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. METHODS: Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. RESULTS: GYY4137 (an H ₂S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. CONCLUSION H ₂S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H ₂S axis. Simultaneously, the Nrf2-controlled CBS/H ₂S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H ₂S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
NF-E2-Related Factor 2/genetics* ; Animals ; Hydrogen Sulfide/pharmacology* ; Rats ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Cell Line ; Uranium/toxicity* ; Antioxidant Response Elements ; Kidney/metabolism* ; Oxidative Stress/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects*

Objective: To establish and validate a whole blood (WB) supply model, thereby providing practical experience for the clinical application of WB in domestic trauma emergency care and informing the development of a wartime blood supply system for the military. Methods: A “10×24” WB supply model was established by formulating blood collection protocols, storage standards, and transfusion criteria. Multiple WB samples were tested under specific storage conditions to assess key indicators at different time points, including red blood cell (RBC), white blood cell (WBC), and platelet counts, hemoglobin concentration, coagulation parameters (PT, APTT, TT, FIB), coagulation factor activity, thromboelastography (TEG) parameters, and electrolyte levels. Additionally, clinical data from hemorrhagic patients who met the criteria for WB transfusion and were admitted between March and July 2024 were analyzed to evaluate WB transfusion volume. Results: RBC counts and hemoglobin levels remained stable in WB stored at 4℃ for up to 10 days. However, platelet counts and coagulation function (PT, APTT) significantly declined with prolonged storage, while potassium levels increased. From March to July 2024, the model was successfully applied to 23 patients with acute hemorrhage, with a median WB transfusion volume of 543 mL. A detailed case study of a severe traumatic hemorrhagic shock patient was reported, who was successfully treated with 5.5 units of refrigerated WB combined with component blood. Conclusion: The “10×24” WB supply model demonstrated acceptable changes in critical quality parameters under strict management and a 10-day rotation cycle. This model effectively supports the treatment of acute hemorrhage and holds promise for integration into the future wartime blood supply system of the military.

Salt plays a critical role in the development of hypertension,which is a major risk factor for damage to target organs such as the heart,brain,and kidneys.Salt sensitivity serves as the fundamental link between salt intake and hypertension.Considerable progress in research on salt-sensitive hypertension has been made regarding the pathogenesis,detection methods and genetic markers;the prevention and treatment of the disease are also constantly improving.Both salt intake and detection rate of salt-sensitive hypertension are relatively high in China.Therefore,exploring the pathogenesis and enhancing detection of salt-sensitive hypertension are crucial for the effective prevention and control of hypertension.

Objective:To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age.Methods:This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage.Results:A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95% CI 2.96-5.79; proteinuria: OR=2.06, 95% CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95% CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95% CI 10.14-23.50; proteinuria: OR=5.80, 95% CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95% CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness ( OR=3.72, 95% CI 2.69-5.12) and proteinuria ( OR=1.67, 95% CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95% CI 7.08-16.61; proteinuria: OR=3.72, 95% CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95% CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95% CI 1.96-2.57; VIM: OR=1.64, 95% CI 1.45-1.86; ARV: OR=1.70, 95% CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95% CI 1.44-1.89; VIM: OR=1.41, 95% CI 1.22-1.63; ARV: OR=1.45, 95% CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion:Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Objective:To compare the effects of different appointment regimens on the daily waiting time, fixedness of treatment time and lateness rate of radiotherapy patients.Methods:Medical records of 5488 radiotherapy from 332 patients on the same linear accelerator in West China Hospital of Sichuan University from March to June 2022 were selected. Based on the radiotherapy information integration platform of MOSAIQ, all patients were randomly assigned to the morning class, afternoon class and evening class. Traditional manual appointment regimen was adopted for the morning class, 30 min appointment regimen for the afternoon class, and 15 min appointment regimen for the evening class, respectively. The differences in patient waiting time for treatment, fixedness of treatment time, and lateness rate under different appointment regimens were compared. The fixedness of treatment time and waiting time was determined by one-way ANOVA, and the 2×3 Chi-square test was adopted for the lateness rate. Results:The waiting time in the 15 min appointment, the 30 min appointment and manual appointment groups were (27.08 ± 17.21), (34.57± 19.12) and (41.50 ±20.94) min, respectively. There was statistical significance among three appointment regimens ( F=254.97, P<0.001). The waiting time was the shortest in the 15 min appointment group, followed by the 30 min appointment group, and the manual appointment group (all P<0.001 for two-group comparison). The fixedness of treatment time in the 15 min appointment, the 30 min appointment and the manual appointment groups were (15.60±7.87), (18.69±8.94) and (24.30±15.10) min, respectively. There was statistical significance among three groups ( F=25.23, P<0.001). Among them, the fixedness of treatment time in the 15 min appointment group was the highest, followed by the 30 min appointment group, and the manual appointment group (all P<0.001). The lateness rates in the 15 min appointment, the 30 min appointment and the manual appointment groups were 5.7%, 6.2% and 9.6%, respectively. The lateness rate in the manual appointment group was higher than those in the 15 min appointment and the 30 min appointment groups ( χ2=19.24、14.90, both P<0.001), but there was no statistical significance in the lateness rate between the 15 min appointment and 30min appointment groups ( χ2=0.39, P=0.535). Conclusion:In the clinical practice of conventional intensity-modulated radiotherapy technology carried out by conventional linear accelerator, the 15 min appointment regimen can shorten the waiting time for radiotherapy and improve the fixedness of daily radiotherapy time, which is worthy of clinical promotion.

Salt plays a critical role in the development of hypertension,which is a major risk factor for damage to target organs such as the heart,brain,and kidneys.Salt sensitivity serves as the fundamental link between salt intake and hypertension.Considerable progress in research on salt-sensitive hypertension has been made regarding the pathogenesis,detection methods and genetic markers;the prevention and treatment of the disease are also constantly improving.Both salt intake and detection rate of salt-sensitive hypertension are relatively high in China.Therefore,exploring the pathogenesis and enhancing detection of salt-sensitive hypertension are crucial for the effective prevention and control of hypertension.

Objective:To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age.Methods:This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage.Results:A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95% CI 2.96-5.79; proteinuria: OR=2.06, 95% CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95% CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95% CI 10.14-23.50; proteinuria: OR=5.80, 95% CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95% CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness ( OR=3.72, 95% CI 2.69-5.12) and proteinuria ( OR=1.67, 95% CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95% CI 7.08-16.61; proteinuria: OR=3.72, 95% CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95% CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95% CI 1.96-2.57; VIM: OR=1.64, 95% CI 1.45-1.86; ARV: OR=1.70, 95% CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95% CI 1.44-1.89; VIM: OR=1.41, 95% CI 1.22-1.63; ARV: OR=1.45, 95% CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion:Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Objective:To compare the effects of different appointment regimens on the daily waiting time, fixedness of treatment time and lateness rate of radiotherapy patients.Methods:Medical records of 5488 radiotherapy from 332 patients on the same linear accelerator in West China Hospital of Sichuan University from March to June 2022 were selected. Based on the radiotherapy information integration platform of MOSAIQ, all patients were randomly assigned to the morning class, afternoon class and evening class. Traditional manual appointment regimen was adopted for the morning class, 30 min appointment regimen for the afternoon class, and 15 min appointment regimen for the evening class, respectively. The differences in patient waiting time for treatment, fixedness of treatment time, and lateness rate under different appointment regimens were compared. The fixedness of treatment time and waiting time was determined by one-way ANOVA, and the 2×3 Chi-square test was adopted for the lateness rate. Results:The waiting time in the 15 min appointment, the 30 min appointment and manual appointment groups were (27.08 ± 17.21), (34.57± 19.12) and (41.50 ±20.94) min, respectively. There was statistical significance among three appointment regimens ( F=254.97, P<0.001). The waiting time was the shortest in the 15 min appointment group, followed by the 30 min appointment group, and the manual appointment group (all P<0.001 for two-group comparison). The fixedness of treatment time in the 15 min appointment, the 30 min appointment and the manual appointment groups were (15.60±7.87), (18.69±8.94) and (24.30±15.10) min, respectively. There was statistical significance among three groups ( F=25.23, P<0.001). Among them, the fixedness of treatment time in the 15 min appointment group was the highest, followed by the 30 min appointment group, and the manual appointment group (all P<0.001). The lateness rates in the 15 min appointment, the 30 min appointment and the manual appointment groups were 5.7%, 6.2% and 9.6%, respectively. The lateness rate in the manual appointment group was higher than those in the 15 min appointment and the 30 min appointment groups ( χ2=19.24、14.90, both P<0.001), but there was no statistical significance in the lateness rate between the 15 min appointment and 30min appointment groups ( χ2=0.39, P=0.535). Conclusion:In the clinical practice of conventional intensity-modulated radiotherapy technology carried out by conventional linear accelerator, the 15 min appointment regimen can shorten the waiting time for radiotherapy and improve the fixedness of daily radiotherapy time, which is worthy of clinical promotion.

ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.