1.High-throughput Sequencing of MET Mutational Landscape in Cancer Patients and the Value of IHC Screening for Targeted Therapy
Feicheng YANG ; Lixia JIANG ; Ruobing LIU ; Kai YANG ; Yewei LI ; Yi XIONG ; Hao DENG ; Jie HU
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(1):172-181
ObjectiveTo investigate the mutation status of the MET gene in tumor patients, with a focus on its expression in lung cancer tissues and its impact on patient prognosis, providing theoretical basis and potential targets for precise diagnosis and treatment of the tumors. MethodsA total of 1,627 tumor patient samples were collected from January 2021 to September 2025. High-throughput sequencing technology was used to conduct DNA-level gene detection on 137 tumor patients with MET mutations. The distribution of mutation sites in exons and introns, as well as the occurrence frequencies of MET gene amplification and gene fusion were analyzed, with particular attention paid to the mutation frequencies of each exon and the high-frequency variant types. Immunohistochemical staining was performed to analyze the expression levels of c-MET protein in tumor tissues of the 137 patients. Immunohistochemical analysis was conducted on tumor tissues of 9 patients with MET gene exon 14 skipping mutations to study the association between c-MET protein expression and this specific mutation type. RNA sequencing results, immunohistochemical staining data, and follow-up prognosis of lung cancer from the GEPIA2 database and TCGA database were comprehensively analyzed to explore the potential relationship between MET gene expression in tumor tissues and patient prognosis. ResultsAmong 1,627 tumor patients, 137 MET mutation patients were detected, including 93 males with an average age of (66.85±9.61) years and 44 females with an average age of (59.43±11.08) years. Lung cancer was the most common tumor type (117 cases). MET gene expression was lower in breast cancer and glioblastoma multiforme, but higher in lung cancer and colorectal cancer as compared with the expression in normal tissues. Survival analysis showed that patients with high MET gene expression in lung adenocarcinoma had a shorter overall survival time than those with low expression. A total of 961 mutations were detected by next-generation sequencing, including 547 exon mutations and 374 intron mutations. MET gene amplification was found in 13 cases and gene fusion in 27 cases. The highest mutation frequency was in exon 2, followed by exon 5, exon 4, and exon 19. High-frequency variant types included c.2890C>A (p.L964M) on exon 4 and c.3028G>T (p.D1010Y) on exon 5. The c-MET protein expression was closely related to the type of gene mutation. Missense mutations often led to positive or strongly positive c-MET protein expression, while nonsense mutations often resulted in weak or absent c-MET protein expression. Among the 9 patients with MET gene exon 14 skipping mutations, the c-MET protein expression score was mostly 0 - 1, with only 1 case scoring 2. Among the 117 lung cancer patients, the incidence rate was higher in males than in females, and more common among stage Ⅲ-Ⅳ patients than among stage I-Ⅱ patients. Out of the 41 patients treated with surgery + targeted drugs (gutemitinib, savolitinib), 8 cases of recurrence or metastasis were found during follow-up. ConclusionMET gene mutations exhibit specific mutation characteristics in different tumor types, and its expression levels show significant differences between various tumor tissues and normal tissues. It is closely related to the poor prognosis of lung adenocarcinoma patients. We found that c-MET protein expression is closely related to the type of MET gene mutation, especially in patients with MET gene exon 14 skipping mutations, which presents a characteristic expression pattern. This provides an important basis for the preliminary screening using immunohistochemistry in clinical practice.
2.The Abnormal Karyotype Spectrum, Disease Correlation and Characteristics of High-frequency Gene Mutations in Patients with Lymphohematopoietic System Diseases
Feicheng YANG ; Jie HU ; Qing HU ; Yanchun LI ; Xiao LIU ; Xiaming TAN
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):306-314
ObjectiveTo analyze the characteristics of chromosomal variations and disease spectrum in patients with lymphohematopoietic system diseases in Hunan region. MethodsA cross-sectional study was conducted, collecting clinical data of 548 patients with lymphohematopoietic system diseases who underwent bone marrow chromosome karyotype analysis at Hunan Provincial People's Hospital from January 2021 to July 2025. G-banding technique was used to detect bone marrow chromosome karyotypes, and chromosome number and structural abnormalities were determined in accordance with the International System for Human Cytogenomic Nomenclature (ISCN) 2024. Retrospective statistical analysis was performed to correlate karyotype abnormality data with disease phenotypes such as myelodysplastic syndrome and acute/chronic leukemia. Classification of the types, frequencies, and reproducibility of variations was calculated to clarify the correlation between karyotypes and disease phenotypes. ResultsAmong the 548 patients who completed bone marrow chromosome karyotype analysis, 127 had chromosomal abnormalities (84 males and 43 females, mean age 58.26 years). Among patients with autosomal abnormalities, 64 cases were detected with translocations (a total of 67 mutations), with t(9;22)(q34;q11.2) (22 cases) and t(15;17)(q24;q21) (10 cases) as high-frequency translocations. Chromosomes 9, 15, etc. were high-frequency variant chromosomes, and 29 cases had complex mutations such as deletions/duplications, with +8 being the common type. There were 27 cases of sex chromosome abnormalities: 7 cases of X chromosome abnormalities (2 cases of chimerism) and 20 cases of Y chromosome deletions (7 cases of 45,X,-Y/46,XY chimerism). Karyotype-disease correlation showed that t(9;22) was detected 9 times in acute leukemia and 8 times in chronic myeloid leukemia; +8, -Y, etc. were associated with multiple types of hematological diseases, and the same karyotype could correspond to multiple disease phenotypes. ConclusionThe high-frequency chromosomal abnormalities, karyotype-disease correlations, and high-frequency NGS genes in patients with lymphohematopoietic system diseases, providing a basis for their precise diagnosis and treatment.
3.Hydrogen Sulfide Alleviates Lipid Peroxidation-Mediated Carbonyl Stress in Uranium-Intoxicated Kidney Cells via Nrf2/ARE Signaling.
Jia Lin LIU ; Min WANG ; Rui ZHANG ; Ji Fang ZHENG ; Xi Xiu JIANG ; Qiao Ni HU
Biomedical and Environmental Sciences 2025;38(4):484-500
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*
4.A blood supply model for the emergency care of severe trauma
Songlin HU ; Zhiyuan WEI ; Gaoxiang HUANG ; Lijuan LIU ; Mingwei FU ; Junke TAN ; Haozhe LI ; Songtao LI
Chinese Journal of Blood Transfusion 2025;38(10):1327-1333
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.
5.Advances in research on salt-sensitive hypertension
Guilin HU ; Hao JIA ; Jianjun MU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):385-392
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.
6.A cohort study on the association between blood pressure trajectories and variability in adolescence and subsequent target organ damage
Tongshuai GUO ; Yue SUN ; Dan WANG ; Guilin HU ; Hao JIA ; Mingfei DU ; Jianjun MU
Chinese Journal of Cardiology 2025;53(1):28-36
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.
7.Comparative study on waiting time and treatment time variability of different appointment regimens for radiotherapy patients
Shoupeng LIU ; Jialu LAI ; Linghui ZHOU ; Yang HUANG ; Juan HU ; Xianghua ZENG ; Zhihong XUE ; Guilin ZENG ; Lang HE
Chinese Journal of Radiation Oncology 2025;34(2):160-166
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.
8.Advances in research on salt-sensitive hypertension
Guilin HU ; Hao JIA ; Jianjun MU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):385-392
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.
9.A cohort study on the association between blood pressure trajectories and variability in adolescence and subsequent target organ damage
Tongshuai GUO ; Yue SUN ; Dan WANG ; Guilin HU ; Hao JIA ; Mingfei DU ; Jianjun MU
Chinese Journal of Cardiology 2025;53(1):28-36
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.
10.Comparative study on waiting time and treatment time variability of different appointment regimens for radiotherapy patients
Shoupeng LIU ; Jialu LAI ; Linghui ZHOU ; Yang HUANG ; Juan HU ; Xianghua ZENG ; Zhihong XUE ; Guilin ZENG ; Lang HE
Chinese Journal of Radiation Oncology 2025;34(2):160-166
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.

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