Objective To explore the changes in serum lactate dehydrogenase （LDH）， monocyte chemoattractant protein-1 （MCP-1）， and transcription factor 4 （TCF4） levels in patients with cerebral small vessel disease complicated by depression and their clinical significance. Methods According to the inclusion and exclusion criteria， 90 patients admitted to the Kailuan General Hospital between January 2022 and August 2024 were selected as the study subjects， including 27 patients diagnosed with cerebral small vessel disease complicated by depression and 63 patients with cerebral small vessel disease uncomplicated by depression. An additional 45 healthy individuals with normal head MRI findings and no mental disorders during the same period at the hospital were selected as the control group. General information was collected from the three groups， including age， body mass index， systolic blood pressure， and diastolic blood pressure.The general information and the levels of serum LDH，MCP-1，and TCF4 in the three groups were compared. The correlations of serum LDH，MCP-1，and TCF4 levels with HAMD score in patients with cerebral small vessel disease and depression were analyzed. Logistic regression was applied to analyze possible factors leading to depression in patients with cerebral small vessel disease.The receiver operating characteristic curve was applied to analyze the efficacy of serum LDH， MCP-1， and TCF4 levels in diagnosing depression in patients with cerebral small vessel disease. Results The levels of serum LDH， MCP-1，and TCF4 were significantly higher in the cerebral small vessel disease complicated by depression group than in cerebral small vessel disease uncomplicated with depression group and the control group （P<0.05）， and these levels were significantly higher in the cerebral small vessel disease uncomplicated with depression group than in the control group （P<0.05）.The serum LDH，MCP-1 and TCF4 were positively correlated with HAMD score in patients with cerebral small vessel disease complicated with depression（r=0.606，0.798，0.672，all P<0.001）.Serum LDH， MCP-1， and TCF4 were influencing factors for depression in cerebral small vessel disease（P<0.05）.The area under the receiver operating characteristic curve of LDH， MCP-1，and TCF4 in combination in the diagnosis of depression in cerebral small vessel disease was 0.917， which was superior to serum LDH， MCP-1， and TCF4 alone （ZLDH-combination=2.457，P=0.014；ZMCP-1-combination=2.384， P=0.017； ZTCF4-combination=2.317， P=0.021）. Conclusion Serum LDH， MCP-1， and TCF4 levels increased in patients with cerebral small vessel disease complicated with depression. Their combination is valuable in the diagnosis of cerebral small vessel disease complicated with depression.
Depression

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective To explore the correlations of serum heat shock protein 70(Hsp70),high-mobility group box 1(HMGB1),glial fibrillary acidic protein(GFAP),and cognitive impair-ment(CI)in patients with cerebral small vessel disease(CSVD).Methods A total of 117 patients with CSVD who were treated at Kailuan General Hospital from July 2023 to July 2024 were selected as study subjects(CSVD group).According to varied scores of the Mini-Mental State Examination(MMSE),they were divided into CI group(54 cases)and non-CI group(63 cases).Additionally,120 healthy individuals who underwent health check-ups during the same period were selected as con-trol group.Clinical data of all subjects were collected.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of Hsp70,HMGB1,and GFAP in serum.The Spearman method was employed to analyze the correlations of serum Hsp70,HMGB1,and GFAP levels with the occurrence of CI in CSVD patients.Logistic multivariate regression analysis was conducted to screen for influencing factors of CI in CSVD patients.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum Hsp70,HMGB1,and GFAP levels for CI in CSVD patients.Results The serum levels of Hsp70,HMGB1,and GFAP in the CSVD group were higher than those in the control group(P＜0.05).There were no significant differences in gender,age,body mass index,smoking history,drinking history,nature of CSVD,education level,triglyc-erides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),Trail Making Test-A(TMT-A),Trail Making Test-B(TMT-B),and low-density lipoprotein cholesterol(LDL-C)between the CI group and the non-CI group(P＞0.05).The levels of uric acid(UA),serum Hsp70,HMGB1,and GFAP in the CI group were higher than those in the non-CI group,while the Montreal Cognitive Assessment(MOCA)score was lower than that in the non-CI group(P＜0.05).The serum levels of Hsp70,HMGB1,and GFAP in CSVD patients were negatively correla-ted with MMSE scores(r=-0.458,-0.525,-0.431,P＜0.05)and MOCA scores(r=-0.462,-0.583,-0.484,P＜0.05).Logistic regression analysis showed that Hsp70,HMGB1,and GFAP were influencing factors for CI in CSVD patients(P＜0.05).The areas under the curve(AUC)for serum Hsp70,HMGB1,and GFAP levels and their combined prediction of cognitive function in CSVD patients were 0.734,0.769,0.766,and 0.902,respectively.The predictive ef-ficacy of the combined prediction was better than that of individual indicators(P＜0.05).Conclu-sion The serum levels of Hsp70,HMGB1,and GFAP are elevated in CSVD patients,which are closely related to the occurrence of CI.The combined detection of these three proteins has a high predictive value for CI in CSVD patients.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

Objective:To explore the medical reference values, distribution characteristics and influencing factors of serum iodine in adults with different thyroid health conditions, and to evaluate the importance of serum iodine in evaluating individual iodine nutrition.Methods:From February 2017 to November 2018, multi-stage stratified cluster sampling was used to select one community and one agricultural (fishing) village in the coastal Yingkou City and the inland areas of Shenyang City of Liaoning Province as survey sites. Cluster sampling of adults over 18 years old who had lived for five years were conducted with questionnaire survey, clinical physical examination and thyroid ultrasound examination. Fasting venous blood samples and one random urine sample were collected from all subjects for serum iodine, thyroid hormone, antibody and urine iodine detection. The 95% medical reference value of serum iodine was established by using the percentage quantile method, and the reference value, distribution characteristics and influencing factors of serum iodine in adults with different thyroid health status were analyzed. The diagnostic value of iodine nutritional indicators in thyroid diseases was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 2 931 adults were surveyed, with serum iodine levels of 62.1 (53.6, 72.2) μg/L, ranging from 5.6 to 642.3 μg/L; urine iodine was 167.6 (111.2, 244.2) μg/L, and the overall iodine level was at an appropriate level. A total of 1 089 patients with thyroid diseases were examined, with a detection rate of 37.2% (1 089/2 931); among them, there were 597 cases of thyroid nodules, 56 cases of endemic goiter, 42 cases of hypothyroidism, 161 cases of subclinical hypothyroidism, 27 cases of hyperthyroidism, 18 cases of subclinical hyperthyroidism, and 474 cases of autoimmune thyroid disease (AITD). There was a statistically significant difference in the detection of thyroid diseases among adults with different levels of serum iodine (χ 2 = 13.80, P < 0.05). The reference values of serum iodine in normal adults, hypothyroidism (without thyroid hormone intervention), hyperthyroidism (without anti thyroid hormone drug treatment), AITD, endemic goiter, and thyroid nodules were 37.2 - 103.0, 12.5 - 52.8, 49.9 - 163.1, 34.3 - 129.3, 27.3 - 92.8, and 37.9 - 119.5 μg/L, respectively. The ROC curve analysis results showed that the serum iodine area under curve(AUC) of patients with hyperthyroidism, subclinical hyperthyroidism, endemic goiter, thyroid nodules, and AITD were 0.94, 0.61, 0.55, 0.53, and 0.52, respectively. The results of univariate analysis showed that there were statistically significant differences in adult serum iodine levels among different positions, regions, age, education level, occupation, iodine intake, blood pressure, and body mass index ( P < 0.05). Conclusions:There are significant differences in serum iodine levels among adults with different thyroid health conditions, and evaluation standards and systems should be developed separately. Serum iodine is an important indicator for evaluating individual iodine nutrition.