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.

ObjectiveTo explore the potential mechanisms of Leigongteng （Tripterygium wilfordii Hook. f.） in treating rheumatoid arthritis （RA） using bioinformatics analysis and experimental validation. MethodsBioinformatics approaches， including the Gene Expression Omnibus （GEO）， the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Gene Ontology （GO） enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， protein-protein interaction （PPI） network analysis， molecular docking， receiver operating characteristic （ROC） analysis， and immune infiltration analysis， were used to predict the key active components of Leigongteng and its target genes for RA treatment. Experimental validation was conducted using human rheumatoid arthritis fibroblast-like synoviocytes （HFLS-RA） in vitro， with methotrexate as the positive control. A scratch assay was performed to assess cell migration after 24 hours of culture. Western blotting was used to detect protein expression levels， qPCR was used to measure target gene mRNA levels， and ELISA was conducted to evaluate inflammatory cytokine levels， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α）. ResultsA total of 117 target genes of Leigongteng were identified and intersected with RA-related genes， yielding 55 key genes. Further screening identified three core genes： PTGS2， CXCR4， and TIMP1. Based on the correspondence between potential drug targets and key components， triptolide and nobiletin were identified as the primary active compounds. Molecular docking results showed that both triptolide and nobiletin had binding energies lower than -5 kcal/mol with their respective target proteins， indicating strong interactions. In vitro experiments demonstrated that， compared with the blank control group， the triptolide， nobiletin， and positive control groups exhibited reduced cell migration rates after 24 hours of culture （P＜0.01）. The expression levels of PTGS2 and CXCR4 （both mRNA and protein） were significantly downregulated， while TIMP1 expression was upregulated. Levels of IL-1β， IL-6， and TNF-α decreased， whereas IL-10 levels increased （P＜0.01）. Compared with the positive control group， the triptolide and nobiletin groups showed increased cell migration rates， upregulated PTGS2 and CXCR4 expression （mRNA and protein）， downregulated TIMP1 expression （mRNA and protein）， increased IL-1β， IL-6， and TNF-α levels， and decreased IL-10 levels （P＜0.05 or P＜0.01）. ConclusionThe key active components of Leigongteng， triptolide and nobiletin， may alleviate RA by inhibiting PTGS2 and CXCR4 while promoting TIMP1 expression， thereby suppressing inflammatory responses.

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:By observing the effects of Calycosin on the proliferation and migration of human renal cancer 769-P cell, to explore the possible molecular mechanism of Calycosin against renal cancer.Methods:769-P cell were cultured with different concentrations of Calycosin [0, 12.5, 25, 50, 100, 200 μmol/L, dissolved in Dimethyl sulfoxide (DMSO)], and the effects of different concentrations of Calycosin on the viability of 769-P cell was detected by CCK8 method. The 769-P cell treated with 200 μmol/L Calycosin were used as the Calycosin group, and the 769-P cell treated with DMSO were used as the control group. The cell colony formation assay and cell scratch assay were used to detect the effects of Calycosin on the proliferation and migration of 769-P cell, respectively. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the effect of Calycosin on the expression of miRNA-1246 and chemokine receptor-4 (CXCR4) in 769-P cell. Western blotting method was used to detect the effects of Calycosin on the expression of CXCR4 and extracellular signal-regulated kinase (ERK) pathway proteins in 769-P cell. Measurement data were expressed as mean ± standard deviation ( ± s), and one-way ANOVA was used for comparison between multiple groups, while t-test was used for comparison between two groups. Results:After cultured with 0, 12.5, 25, 50, 100, and 200 μmol/L of Calycosin, the absorbance values of renal cancer 769-P cell were 0.99 ± 0.06, 0.74 ± 0.07, 0.60 ± 0.03, 0.55 ± 0.05, 0.40 ± 0.06, 0.21 ± 0.04, respectively; compared with 0 μmol/L, the Calycosin could reduce the survival rate of 769-P cell ( P<0.05). The number of clones of 769-P cell in the control group and the Calycosin group was 109.80 ± 13.19 and 60.66 ± 11.22, respectively, and the number of clones of the 769-P cell in the Calycosin group was decreased, the difference was statistically significant ( t=5.67, P<0.01). The relative migration rates of 769-P cell in the control group and the Calycosin group were (43.13 ± 3.82)% and (14.27 ± 3.25)%, respectively, after the 769-P cell were treated with Calycosin, the cell migration ability was weakened ( t=5.71, P<0.05). The relative expression levels of miRNA-1246 in 769-P cell of the control group and the Calycosin group was 1.03 ± 0.12 and 6.99 ± 1.84, respectively, and the relative expression levels of CXCR4 mRNA was 7.17 ± 2.96 and 0.98 ± 0.06, respectively, showed that Calycosin can up-regulate the expression of miRNA-1246 in 769-P cell ( t=3.24, P<0.01), and down-regulate the expression of CXCR4 mRNA ( t=4.18, P<0.01). Compared with the control group, the Calycosin could down-regulate the expression of CXCR4 protein and ERK pathway protein in 769-P cell. Conclusion:Calycosin can inhibit the proliferation and migration of renal cancer 769-P cell, and its mechanism may be related to up-regulating the expression of miRNA-1246 and blocking the CXCR4/ERK pathway.

Objective To comparatively explore the prognosis of hepatocellular carcinoma(HCC)patients with hepatitis B(HB)and hepatitis C(HC)after microwave ablation(MWA).Methods Data of 159 HCC patients with HB(HB-HCC)and 159 HCC patients with HC(HC-HCC)who received MWA treatment were retrospectively collected.The oncologic outcomes were compared between groups,the causes of death were analyzed,and the risk factors of overall survival(OS)in HCC patients after MWA were observed.Results The OS rate in HC-HCC group was lower than that in HB-HCC group(P=0.045),while no significant difference of disease free survival rate(P=0.095)nor cancer specific survival rate(P=0.180)was found between groups.Compared with HB-HCC group,HC-HCC group had higher risk of death due to complications related to liver cirrhosis(HR=2.339,P=0.043).Child-Pugh class B(HR=3.082,P＜0.001),hepatitis viral load＞500 IU/ml(HR=1.654,P=0.006)and the maximum diameter of lesion≥3.0 cm(HR=1.541,P=0.017)were all independent risk factors of OS in HCC patients after MWA.Conclusion Compared with HB-HCC patients,HC-HCC patients had shorter OS after MWA.

Objective:To investigate the cognitive functions of temporal lobe epilepsy (TLE) patients with bilateral asynchronous interictal discharges.Methods:A total of 162 TLE patients who were treated at Zhongshan Hospital, Fudan University, from June 2021 to December 2023 were collected. According to the interictal scalp electroencephalogram, TLE patients were classified to the TLE with bilateral temporal asynchronous interictal epileptiform discharges ( n=51) and TLE with unilateral temporal epileptiform discharges ( n=111). Unilateral TLE patients were divided into TLE with right ( n=48) and left ( n=63) temporal epileptiform discharges. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Digital Span (DS), Verbal Fluency Test (VFT), the third part of Color Word Test (CWT-C), Trail Making Test-B (TMT-B), Symbol Digit Modalities Test (SDMT), Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure (ROCF), and Similarity Comprehension Test were performed for the participants. The differences of cognitive functions between patients with bilateral and unilateral temporal discharges were compared. Univariate and multivariate Logistic regression models were used to analyze the risk factors for patients with bilateral temporal asynchronous discharges. Spearman analysis was used to explore the correlation between cognitive function and clinical indicators. Results:In the group of TLE patients with bilateral asynchronous discharges compared to those with unilateral discharges, the completion time of CWT-C [67 (55, 103) s vs 59 (50, 71) s, Z=-2.904, P=0.004], TMT-B [159 (108, 219) s vs 129 (95, 180) s, Z=-2.361, P=0.018] was longer. Additionally, TLE patients with bilateral asynchronous discharges got lower scores of MMSE [28 (26, 29) vs 29 (28, 30), Z=3.098, P=0.002], MoCA [23 (19, 28) vs 27 (23, 28), Z=3.175, P=0.001], AVLT1+2+3 [16.843±6.482 vs 19.162±5.526, t=-2.347, P=0.020], AVLT6 [6 (3, 10) vs 8 (5, 10), Z=3.275, P=0.001], ROCF2 [15 (8, 22) vs 20 (12, 25), Z=2.870, P=0.004], ROCF3 [14 (8, 22) vs 20 (11, 25), Z=2.634, P=0.008], and Similarity Test [13 (8, 18) vs 16 (12, 20), Z=2.387, P=0.017] as well as lower VFT-vegetable and fruit count [15 (13, 19) vs 18 (15, 21), Z=2.402, P=0.016] and SDMT completion count [41 (30, 53) vs 51 (40, 60), Z=3.089, P=0.002]. The multivariate Logistic regression analysis showed that the decrease in AVLT6 scores ( OR=1.546, 95% CI 1.150-2.078, P=0.004) and longer TMT-B time ( OR=1.013, 95% CI 1.001-1.025, P=0.035) were independent risk factors for TLE patients with bilateral asynchronous discharges. Conclusions:Compared to the patients with TLE characterized by unilateral temporal lobe discharges, those with asynchronous discharges in bilateral temporal lobes show statistically significant declines in all domains of cognitive functions, including executive function, memory, and language abilities. Decreased cue recall ability in language memory and prolonged trail-making test in executive function are independent cognitive impairment risk factors for bilateral temporal asynchronous discharges.

Objective:To analyze the clinical characteristics and risk factors of acute kidney injury (AKI) in portal venous hypertension patients undergoing transjugular intrahepatic portosystemic shunt (TIPS).Methods:It was a retrospective observational study. In this study, the clinical data of portal venous hypertension patients undergoing TIPS at Beijing Shijitan Hospital, Capital Medical University from October 16, 2020 to March 30, 2022 were collected retrospectively. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group. The clinical characteristics of the patients were compared between the two groups, and multivariate logistic regression was used to analyze the risk factors of AKI.Results:A total of 384 patients undergoing TIPS were included in this study, whose age was (53.17±13.35) years. Among them, 122 (31.8%) were female, and 32 patients (8.3%) had AKI. Compared to the non-AKI group, the proportion of patients with diabetes mellitus, baseline estimated glomerular filtration rate (eGFR) <60 ml·min -1·(1.73 m 2) -1 and intraoperative hypotension, Child-Pugh score of liver function, preoperative serum creatinine, preoperative blood uric acid, and postoperative portal venous pressure gradient (PPG) were higher in AKI group (all P<0.05), while the levels of hemoglobin and serum albumin were lower (both P<0.05). Multivariate logistic regression results showed that combined diabetes ( OR=3.728, 95% CI 1.262-11.013, P=0.017), baseline eGFR<60 ml·min -1·(1.73 m 2) -1( OR=3.571, 95% CI 1.356-9.400, P=0.010), decreased serum albumin ( OR=0.847, 95% CI 0.738-0.972, P=0.018), increased PPG after TIPS ( OR=1.096, 95% CI 1.002-1.200, P=0.045) and intraoperative hypotension ( OR=7.006, 95% CI 2.023-24.195, P=0.002) were independently associated with postoperative AKI in portal venous hypertension patients undergoing TIPS. Until discharge, 6 patients with AKI (18.8%) had complete renal function recovery, 24 patients (75.0%) partially recovered, and 2 patients (6.3%) did not recover. The length of hospital stay, hospitalization costs, and all-cause mortality in AKI patients were significantly higher than those in the non-AKI group ( P<0.05, respectively). Conclusions:AKI is not uncommon in patients receiving TIPS. The classical risk factors of AKI, such as diabetes and baseline renal dysfunction, and the factors affecting volumes like lower serum albumin level, hypotension during the operation, and higher PPG level are closely related to the incidence of AKI in these patients. AKI significantly increases the all-cause mortality and medical expenses, which is worth early prevention and treatment by clinicians.

Objective:To investigate the changes and associated factors of cerebral blood flow in middle-aged and elderly patients undergoing maintenance hemodialysis (MHD).Methods:This was a prospective observational study. End-stage renal disease (ESRD) patients undergoing MHD aged over 50 years at Beijing Shijitan Hospital, Capital Medical University from January 2023 to June 2023 were included. General clinical data of the selected individuals were collected, and dialysis related indicators were recorded and calculated. Mean flow velocity (MFV) of the middle cerebral arterial was measured by transcranial Doppler sonography (TCD) to represent cerebral blood flow throughout dialysis. Hemodialysis-related variables were collected. The MFV values of bilateral middle cerebral artery were measured through temporal windows at 7 time points: 15 minutes before dialysis (T1), 15 minutes (T2), 30 minutes (T3), 60 minutes (T4), 120 minutes (T5), 180 minutes (T6) during dialysis, and the endpoint of dialysis (T7), and the average values were recorded. The ΔMFV was calculated as pre-minus endpoint values of MFV. The Spearman rank correlation method was used to analyze the correlations between ΔMFV and dialysis-related variables, and multiple linear regression method was used to analyze the related factors of the changes in MFV.Results:This study included a total of 123 patients undergoing MHD, aged (63.63±8.44) years (range 50-85 years), including 99 males (80.5%). TCD examination demonstrated a decline trend in MFV throughout dialysis. The MFV at T7 was significantly lower than that at T1 ( Z=-7.650, P<0.001). The Spearman correlation analysis showed that the decline in MFV was correlated with ultrafiltration volume ( r=0.356), ultrafiltration rate ( r=0.371), the difference in systolic pressure (pre-analysis minus post-dialysis, r=0.251), the difference in mean arterial pressure (pre-dialysis minus post-dialysis, r=0.194), combined diabetes ( r=0.293), dialysis vintage ( r=0.220), Kt/V ( r=0.287), and serum albumin ( r=-0.295). Multiple linear regression analysis showed that combined with diabetes ( B=3.889, 95% CI 1.373-6.405, P=0.003), decreased serum albumin ( B=-0.456, 95% CI -0.877--0.036, P=0.034), increased ultrafiltration rate ( B=11.099, 95% CI 6.402-15.797, P<0.001) and the decline in systolic pressure ( B=0.062, 95% CI 0.008-0.116, P=0.026) were significantly associated with the decline in MFV throughout dialysis. Conclusions:In middle and elderly patients with ESRD undergoing hemodialysis, there is a decline trend in cerebral blood flow during hemodialysis. The combination of diabetes, lower serum albumin, higher ultrafiltration rate, and intradialytic systolic pressure decline are the risk factors influencing the intradialytic decline of cerebral blood flow.