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 observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

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 analyze the clinical evolution and atypical spinal cord MRI features of myelitis post severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Methods Four patients with myelitis post the SARS-CoV-2 infection were retrospectively analyzed regarding the clinical manifestations,the dynamic changes of the spinal cord MRI and the treatment outcomes.Results The time latencies from SARS-CoV-2 infection to the onset of myelitis of the 4 patients were 5 d,15 d,80 d,and 30 d,respectively.The onset symptoms were numbness and weakness of lower limbs in 3 patients,and back pain with weakness of lower limbs in 1 patient.The peak symptoms included paraplegia,sphincter dysfunction,sensory plane and spastic gait.The expanded disability status score(EDSS)of the 4 patients were 7.5,9.0,9.0 and 7.5,respectively.Initial spinal cord MRI showed normal in 1 case,linear meningeal enhancement in 1 case,and punctate T2 signal changes in 2 cases.Spinal cord MRI at the peak of the symptoms showed patchy,linear and cloudy-like high signals on sagittal T2,which mainly distributed in lateral and posterior cords on axial T2.The prominent features of the MRI findings were the linear meningeal enhancement that appeared in all 4 cases during the disease and their mismatch with the severity of clinical symptoms.Two of the four patients received pulse methylprednisolone combined with plasma exchange therapy and did not show significant improvement,and all 4 patients were left with significant disability.Conclusions Myelitis post SARS-CoV-2 infection usually presents typical symptoms of myelitis,while the spinal cord MRI presents patchy,linear and cloudy-like high signals,with linear meningeal enhancement.The delayed and atypical spinal cord MRI findings need additional attention.

Objective:To investigate the effect of problem-solving therapy (PST) on clinical efficacy, cognitive and social function in senile patients with first episode depression.Methods:From March 2020 to August 2021, a total of 86 patients with first onset elderly depression treated in the geriatric department of Qingdao Mental Health Center were selected. According to the random number table method, totally 86 patients were randomly divided into a study group and a control group, with 43 cases in each group. The control group was treated with antidepressant drugs and basic psychiatric nursing intervention. The study group received PST treatment on the basis of the control group for 8 weeks. The Hamilton depression scale-17 items(HAMD-17), Montreal cognitive assessment scale (MoCA), and social dysfunction screening scale (SDSS) were used to assess the degree of depression, cognitive function and social function in both groups. SPSS 18.0 was used for statistical analysis. Independent sample t-test was used for comparison between groups, paired sample t-test was used for comparison before and after treatment. Results:After 8 weeks of intervention, HAMD-17 scores and SDSS scores in the two groups were both significantly decreased compared with before intervention, and the differences between pre intervention and post intervention had statistical significance( t=3.067, 22.543, both P<0.05), while MoCA scores were significantly increased, and the difference between pre intervention and post intervention had statistical significance ( t=9.623, P<0.05). Compared with the control group after 8 weeks of intervention, the HAMD-17 score ((14.44±1.97), (15.58±2.66), t=2.260, P=0.026) and SDSS score((9.44±2.24), (13.00±1.73), t=8.242, P<0.001) of the study group were lower, and the score of MoCA ((25.44±1.28), (23.84±1.56), t=5.223, P<0.001) was higher. Conclusion:In addition to conventional antidepressant therapy, PST not only reduces the severity of depression in elderly patients with first episode depression, but also significantly improves their cognitive and social function.

Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.

ObjectiveTo explore the characteristics of circadian rhythm of blood pressure in patients with masked hypertension （MH） and its relationship with twelve two-hour peirods， providing a basis for early detection and intervention of MH. MethodsPatients who underwent 24-hour ambulatory blood pressure examination in the ambulatory blood pressure room of Jiangsu Province Hospital of Chinese Medicine from January to December 2022 were enrolled， and according to their outpatient blood pressure measurements， 24-hour ambulatory blood pressure monitoring and follow-up survey results， the MH， essential hypertension （EH） and normal blood pressure groups were classified， with 50 cases in each group. The general data， office blood pressure and 24-hour ambulatory blood pressure monitoring data were collected. The circadian rhythm of blood pressure including 24-hour average systolic blood pressure （24h SBP）， daytime average systolic blood pressure （d SBP）， nighttime average systolic blood pressure （n SBP）， 24-hour average diastolic blood pressure （24h DBP）， daytime average diastolic blood pressure （d DBP）， and nighttime average diastolic blood pressure （n DBP） were compared among the groups， and the nighttime blood pressure dipping percentage was calculated. The type of circadian rhythm was determined based on the nighttime blood pressure dipping percentage. The variability of blood pressure including 24h SBP standard deviation （24h SBP-SD）， d SBP standard deviation （dSBP-SD）， n SBP standard deviation （nSBP-SD）， 24h DBP standard deviation （24h DBP-SD）， d DBP standard deviation （dDBP-SD）， and n DBP standard deviation （nDBP-SD） were compared among groups， and the corresponding coefficient of variation （CV）， that is， 24h SBP-CV， d SBP-CV， n SBP-CV， 24h DBP-CV， d DBP-CV and n DBP-CV， were calculated. Based on the 24-hour ambulatory blood pressure monitoring results， the twelve two-hour average SBP and DBP in each group were calculated and compared. Simultaneously， patients with EH were divided into grades 1， 2， and 3 for further stratified analysis. ResultsThe age of the MH group was significantly higher than that of the EH group and the normal blood pressure group （P＜0.01）. The body mass index （BMI） and the proportion of smoking and alcohol consumption in the MH group and the EH group were significantly higher than those in the normal blood pressure group （P＜0.05 or P＜0.01）. In the normal blood pressure group， there were 49 dipper patterns （98.0%） and one non-dipper pattern （2.0%）； in the MH group， there were two dipper patterns （4.0%）， 29 non-dipper patterns （58.0%） and 19 reverse-dipper patterns （38.0%）； in the EH group， there were 20 dipper patterns （40.0%）， 23 non-dipper patterns （46.0%） and seven reverse-dipper patterns （14.0%）. Compared to the normal blood pressure group， the groups of MH and EH had significantly decreased proportion of dipper pattern and increased proportion of non-dipper and reverse-dipper pattern （P＜0.01）； the proportion of dipper pattern in the MH group was lower than that in the EH group， while the proportion of reverse-dipper pattern was higher （P＜0.01）. Compared to those in the normal blood pressure group， n SBP and n DBP in the MH group， as well as the the average SBP and average DBP at Zi hour （子时， 23：00-1：00）， Chou hour （丑时， 1：00-3：00）， Yin hour （寅时， 3：00-5：00）， Mao hour （卯时， 5：00-7：00） and average SBP at Hai hour （亥时， 21：00-23：00） in the MH group increased，while the average DBP at Si hour （巳时， 9：00-11：00） decreased （P＜0.01）； 24h SBP， 24h DBP， d SBP， d DBP， n SBP， and n DBP，d SBP-SD， n SBP-SD，n DBP-SD increased， as well as the average SBP and average DBP at twelve two-hour periods increased in the EH group，while the 24h SBP-CV， 24h DBP-CV，and d DBP-CV in the EH group decreased（P＜0.05 or P＜0.01）. The EH group had higher 24h SBP， 24h DBP， d SBP， d DBP， n SBP， n DBP， 24h DBP-SD and n DBP-SD ， as well as higher average SBP and DBP at all twelve two-hour periods， and lower d DBP-CV than the MH group（P＜0.05 or P＜0.01）. The EH group had 18 cases of grade 1 （36.0％）， 19 cases of grade 2 （38.0％） and 13 cases of grade 3 （26.0％）， with no significant differences among groups （P＞0.05）. ConclusionThe circadian rhythm of blood pressure in MH patients are mostly non-dipper and reverse-dipper patterns， and the abnormal elevation of blood pressure is obvious at Zi hour， Chou hour， Yin hour and Mao hour （23：00-7：00）.

To have better clinical understanding of Schimke immuno-osseous dysplasia(SIOD) through analyzing the clinical features, treatment, and prognosis of four patients with SIOD.