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.

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 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.

Liver cancer is a prevalent and highly malignant cancer worldwide,with 90％of cases being hepatocellular carcinoma,presenting a significant risk to human health.As early-stage liver cancer often lacks specific manifestations,most patients with liver cancer are already in the middle and late stage of the disease when liver cancer is diagnosed,thus,missing the opportunity for optimal radical treatment.However,the exploration of the treatment for middle and advanced primary hepatocellular carcinoma has never ceased.In recent years,transarterial chemoembolization(TACE)has been included in the standard treatment regimens for primary hepatocellular carcinoma.With the advancement of multidisciplinary comprehensive treatment,various treatment options to reduce the burden of liver cancer lesion with satisfactory therapeutic results have been reported and have been widely used in clinical practice,e.g.hepatic artery infusion chemotherapy(HAIC),targeted therapy,and immunotherapy in combination with TACE,which have significantly improved the overall survival of patients with liver cancer.This paper aims to make a comprehensive review about the latest progress of combination use of TACE and other therapies in reducing tumor burden and improving patient survival in the treatment of primary hepatocellular carcinoma,and to summarize the key issues in combination therapy that require more in-depth research.(J Intervent Radiol,2024,33:688-692)

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Objective:To investigate the effect of Relative Bedrest Condition Morita Therapy(RBCMT) on the improvement of depression and anxiety symptoms and personality in patients with recurrent depression disorder.Methods:Seventy patients with recurrent depressive disorder hospitalized in Kailuan Mental Health Center were randomly divided into study group and control group( n=35 in each group) from June to October, 2019.The study group was given RBCMT on the basis of conventional treatment and nursing.The Eysenck personality questionnaire (EPQ), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were used to assess the clinical symptoms and personality characteristics of the patients and to analyze and compare them. Results:(1) EPQ score in each dimension: There were significant differences within group among different time in introverted and extroverted dimension (study group: baseline: 46.14±10.99, the fifth weekend: 50.43±8.86, the eighth weekend: 53.86±7.08, F=6.291, P=0.003.Control group: baseline: 45.29±8.99, the fifth weekend: 48.29±8.31, the eighth weekend: 50.29±7.57, F=3.211, P=0.044) and neuroticism dimension score (study group: baseline: 60.14±5.49, the fifth weekend: 53.29±4.53, the eighth weekend: 50.57±4.33, F=36.809, P<0.001.Control group: baseline: 60.29±6.18, the fifth weekend: 55.86±6.00, the eighth weekend: 53.14±5.30, F=13.353, P<0.001) among different time points in the group.Neuroticism scores between the two groups at the same time were statistically significant(the fifth weekend: F=4.095, P=0.047, the eighth weekend: F=4.940, P=0.030). After 8 weeks of inclusion, there was a statistically significant difference between the two groups in the score of introverted and extroverted dimension ( F=4.157, P=0.045). There was no significant difference in the score of spiritual quality dimension at different time within the group or at the same time point between the groups.(2)HAMD score: There were statistically significant differences within group among different time(study group: baseline: 32.00±4.04, the fifth weekend: 15.23±5.01, the eighth weekend: 9.31±3.15, F=282.376, P<0.001.Control group: baseline: 31.91±4.59, the fifth weekend: 17.86±5.11, the eighth weekend: 11.17±3.64, F=195.019, P<0.001), and the differences between the two groups at the same time were statistically significant (the fifth weekend: F=4.724, P=0.033, the eighth weekend: F=5.205, P=0.026). (3)HAMA score: There were statistically significant differences within group among different time(study group: baseline: 18.69±8.87, the fifth weekend: 10.34±5.34, the eighth weekend: 7.97±2.98, F=28.679, P<0.001.Control group: baseline: 18.60±8.02, the fifth weekend: 13.31±6.35, the eighth weekend: 10.37±4.86, F=14.241, P<0.001). The difference between the two groups at the same time point was statistically significant (the fifth weekend: F=4.161, P=0.045, the eighth weekend: F=8.315, P=005). (4)Multiple linear regression results indicated that RBCMT ( β=-0.312, t=-2.360, P=0.022) and introverted and extroverted dimension personality ( β=-0.334, t=-2.355, P=0.022) were the influencing factors of HAMA. Conclusion:Compared with the conventional treatment, the Relative Bedrest Condition Morita Therapy can reduce the anxiety symptoms and improve the depressive symptoms by enhancing the extraversion personality characteristics of the patients.