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 investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

Objective:To summarize the relevant evidence of exercise intervention for patients with multiple myeloma at home and abroad, and provide evidence-based basis for medical staff to formulate exercise intervention programs.Methods:Through the method of evidence-based nursing, the literatures related to exercise intervention for patients with multiple myeloma were systematically retrieved from relevant guideline websites, professional association websites and databases at home and abroad, including best practices, recommended practices, guidelines, expert consensus, evidence summary, systematic reviews and so on. The search time limit was established until April 16, 2024. Two researchers evaluated the quality of the literature and extracted the data. JBI pre-classification of evidence and level of Recommendation system (2014 version) was used to determine the level of evidence items and recommendation level.Results:A total of 15 articles were included, including 1 clinical decision, 4 guidelines, 8 systematic reviews, 1 expert consensus and 1 evidence summary. A total of 26 pieces of evidence were summarized, including 5 aspects, including applicable population, exercise evaluation, exercise plan, exercise precautions and exercise management.Conclusions:The best evidence summarized in this study provides a basis for the development and management of exercise intervention in patients with multiple myeloma. It is suggested that clinical staff should fully consider the clinical context when applying the evidence, and develop personalized exercise intervention programs based on the patient′s status and preferences.

Objective:To analyze the impact of hypertension prevention and control on the mortality rate of acute myocardial infarction (AMI) in Tengzhou City, Shandong Province from 2013 to 2021.Methods:This study was a cross-sectional study. The surveillance data of AMI deaths from January 1, 2013 (the time when hypertension prevention and control began in Tengzhou) to December 31, 2021 were collected in the coronary heart disease information management system, the mortality rate of AMI and its change trend were analyzed, and the distribution differences among residents with different characteristics were analyzed. The registered population information was obtained from Tengzhou Public Security Bureau, and the age and gender standardized mortality rate was calculated based on the data of the 7th national population census in 2020. The t test was used to compare the differences in blood pressure and laboratory items, chi-square test was used to compare the differences in mortality rate, and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate, so as to analyze the impact of hypertension prevention and control on the mortality rate of AMI. Results:The overall crude and standardized AMI mortality rates in Tengzhou decreased from 50.87/100 000 and 63.82/100 000 to 41.08/100 000 and 38.70/100 000 from 2013 to 2021, respectively ( Z=-5.741, -10.884, both P<0.001), and double peaks were formed in 2014 and 2017. The first peak of crude and standardized mortality rate was formed in 2015 for males, which was 25.12% and 17.60% higher than that in 2013; and the first peak was formed in 2014 for females, which was 29.56% and 24.38% higher than that in 2013 ( χ2=13.200, 9.065, 14.862, 12.123) (all P<0.05). The second peaks of crude and standardized mortality were formed in 2017, with an increase of 18.17% and 17.17% for males and 25.73% and 22.34% for females from 2016 ( χ2=8.266, 9.182, 14.066, 11.105), the standardized mortality rate was 15.18%-29.01% higher in males than that in females ( χ2=6.239-19.326) (all P<0.05). The mortality rate of AMI increased with age ( Z=35.485-51.308) ( P<0.001). Compared with 2013, the mortality rate in males aged 55 to 64 years in 2015 increased by 64.29% from that in 2013, and that of females in 2017 increased by 108.48% from that in 2015; and that in females aged 35 to 44 years in 2016 increased by 373.51% from that in 2015 ( χ2=10.751, 12.805, 4.799); in 2021, the age group of male and female≥65 years decreased by 43.51% and 41.28% when compared with that in 2013, respectively ( Z=-7.333, -7.465) (all P<0.05). The mortality rate of AMI in urban areas decreased by 76.93% in 2021 when compared with that in 2016, and in rural areas it decreased by 30.28% than that in 2017. Both regions showed a downward trend ( Z=-7.560, -2.398) (both P<0.05). Conclusions:The mortality rate of AMI in Tengzhou City, Shandong Province from 2013 to 2021 shows a decreasing trend, and prevention and control of hypertension may be one of the reasons. The standardized mortality rate of males is higher than that of females, and the mortality rate decline rate in rural areas is lower than that in urban areas. The primary and secondary prevention of AMI in such populations should be strengthened.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

Objective To explore the property of projection neurons in the pathway from the medial prefrontal cortex(mPFC)to the thalamic paraventricular nucleus(PVT)and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice.Methods Three knock-in mice with glutamate decarboxylase 67-green fluorescent protein(GAD67-GFP)were used in morphological tracing experiments,and twenty-seven C57 mice were used for behavioral observation experiments.Cholera toxin subunit B(CTB)was injected into the PVT of GAD67-GFP transgenic mice,and the properties of mPFC neurons projected to PVT were observed.The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain,such as mechanical pain,thermal pain,cold pain,and on acute inflammatory pain induced by capsaicin in mice.Results CTB-labeled neurons in the mPFC were mainly distributed in layer Ⅴ and layer Ⅵ and not double-labeled with GAD67-GFP.Chemogenetic activation of the mPFC-PVT pathway decreased the mechanical pain threshold significantly(P＜0.0001)and shortened the thermal pain latency(P＜0.001),but had no obvious effects on cold pain.Inhibition of this pathway increased the mechanical pain threshold significantly(P＜0.05).Activation of the pathway increased the paw licking time(P＜0.05)in acute inflammatory pain induced by capsaicin.Conclusion mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain,thermal pain,and acute inflammatory pain induced by capsaicin in mice.