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 effects of two methods of smear layer removal on the surface properties of dentin. METHODS: Sixty extracted sound third molars were collected in this study, and were prepared as uniform dentin specimens with smear layer. All specimens were randomly divided into three groups: Control group, ultrasonic treatment (UT) group and etched treatment (ET) group. Scanning electron microscope (SEM) were used to observe the surface micromorphology of all three groups. Then, the surface elements, mineral phases and functional groups were analyzed by energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and flourier transformed infrared spectrometer (FTIR) respectively. The mechanical properties, hydrophilicity and biocompatibility were also further evaluated. RESULTS: It was revealed that dentin tubules of UT and ET groups were exposed, but lots of dentin debris piled up on the surface of the control one which covered up dentin tubules on the surface. The EDX results should that the weaker peak value of calcium and phosphorus in ET group than control and UT groups. Characteristic peaks of hydroxyapatite could be seen by XRD in all of the three groups, but lower distinctive peaks of amide Ⅰ, Ⅱ and Ⅲ bands of collagen of the dentin surface in control group than in ET and UT groups. The microhardness results showed that ET group was lower than control and UT groups, the difference was significant (P < 0.05). Better hydrophilicity of ET group was investigated (P < 0.05) than control group and UT group. Cells could be observed to adhere normally to dentin surface of each group which meant that all of the three groups had good biocompatibility. CONCLUSION Both UT and ET could effectively remove the smear layer on the surface of dentin and had no adverse effect of the dentin micromorphology and biocompatibility. The ultrasonic removal of the smear layer did not influence the mineral structure, hydrophilicity and mechanical properties of dentin surface. Although ET can effectively improve the hydrophilicity of dentin but decreased mechanical properties and the content of calcium and phosphorus.
Dentin/ultrastructure* ; Humans ; Surface Properties ; Smear Layer ; Molar, Third ; Microscopy, Electron, Scanning ; Dental Etching/methods*

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.

OBJECTIVE To provide standardized guidance for the clinical application and management of biosimilars， and promote their widespread and rational use in clinical treatment. METHODS The design， planning， and drafting process as well as the full report of Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） followed the WHO Handbook for Guideline Development （2nd edition）， which fully considered the best current evidence from evidence-based medicine， multidisciplinary expert experience， and patient preferences and values. Grading of Recommendations Assessment， Development， and Evaluation （GRADE） approach was adopted to evaluate the quality of evidence and determine the strength of recommendations. RESULTS & CONCLUSIONS Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） presented 10 recommendations including 7 strong recommendations and 3 weak recommendations. The recommendations covered the entire process of clinical application and management of biosimilars. Medical institutions and relevant health regulatory departments can refer to this guideline for the scientific management of the extrapolation of unapproved indications of biosimilars. Healthcare providers can refer to this guideline for pre-treatment assessments， patient education， pre-treatment regimen before administration， and dosage regimen adjustments. Multidisciplinary medical teams can refer to this guideline to provide pharmacovigilance and patient management throughout the treatment process.

BACKGROUND:Unicompartmental knee arthroplasty has been paid more and more attention because of its advantages of fewer traumas,less blood loss,less complications,faster recovery,excellent knee function and high prosthetic survival rate.Most of the relevant reports focused on its clinical effect,but the changes in the levels of relevant inflammatory cytokines in patients after unicompartmental knee arthroplasty were rarely reported. OBJECTIVE:To investigate the effect of unicompartmental knee arthroplasty in patients with medial compartment osteoarthritis of the knee and the changes of interleukin-1,interleukin-6,and tumor necrosis factor-α levels. METHODS:A total of 30 patients with medial compartment osteoarthritis of the knee who received unicompartmental knee arthroplasty from September 2021 to March 2023 and met the inclusion criteria were selected as the study subjects.Medial angle of proximal tibia,femoral and tibial angle,pain visual analog scale score,hospital for special surgery score,knee joint range of motion,synovial fluid interleukin-1,interleukin-6,and tumor necrosis factor-α levels before and after surgery were compared and statistically analyzed. RESULTS AND CONCLUSION:(1)All 30 patients had grade I wound healing.All patients were followed up for more than 6 months after surgery.There were no complications such as prosthesis loosening and dislocation of prosthesis liner in all patients.(2)The medial proximal tibia angle and the femoral and tibial angles measured after operation were significantly improved(P<0.05).(3)The visual analog scale score,hospital for special surgery score and range of motion measured at 1,3,and 6 months after operation were better than those before operation(P<0.05),and showed a gradual improvement(P<0.05).(4)The levels of interleukin-1,interleukin-6,and tumor necrosis factor-α in synovial fluid at 3 and 6 months after operation were decreased gradually compared with those before operation(P<0.05)and showed a gradual downward trend at each time point after operation.(5)It is indicated that unicompartmental knee arthroplasty can effectively treat medial compartment osteoarthritis of the knee,significantly relieve pain,restore knee joint function,improve knee varus deformity and lower limb strength line,and reduce the levels of inflammatory cytokines interleukin-1,interleukin-6,and tumor necrosis factor-α in joints to a certain extent.

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS)on the symptom treatment of adolescent depressed patients and the regulatory effect of serum inflammatory factors and cranial nerve factors.Methods A total of 110 adolescent patients with depression were analyzed from May 1,2022 to May 30,2023,including 55 in the observation group and 55 in the control group.emotional intelligence scale(EIS),the Hamilton depression scale(HAMD)and World Health Organization quality of life bref(WHOQOL BREF)were used to evaluate the emotional intelligence,depression and quality of life before treatment and 1.5 and 3.0 months after treatment.Serum 5-hydroxytryptamine(5-HT),glial fibrillary acidic protein(GFAP),brain-derived neurotrophic factor(BDNF),interleukin(IL)-1β,IL-6 and transforming growth factor(TGF)-β1 were detected,and the protein expression levels of IL-1β,IL-6 and TGF-β1 in peripheral blood cells were detected by Western blot.Results After 1.5 and 3.0 months of intervention,the EIS score and WHOQOL-BREF scores in were increased,and the observation group was higher than that of the control group(P＜0.01),and the HAMD score was lower than that of the control group(P＜0.01).After treatment,the levels of BDNF,5-HT and GFAP in the observation group were higher than those in the control group(P＜0.01).The levels of IL-1β and IL-6 were lower in the observation group,and the levels of TGF-β1 were higher(P＜0.01).Conclusion rTMS stimulation can further down-regulate the expression of pro-inflammatory factors(IL-1β,IL-6)and anti-inflammatory factors(TGF-β1)and cranial nerve factors(BDNF,GFAP,5-HT)in patients on the basis of basic drug treatment,so the use of rTMS stimulation in the treatment of adolescent depression has certain clinical application value.

Objective To construct a rational and efficient bed resource allocation management model to reduce pre-hos-pital waiting times,ensure patient safety,and improve satisfaction.Methods Based on lean management principles,a bed re-source allocation management model was developed and continuously optimized.The study compared bed turnover rates and effi-ciency indices,as well as preoperative waiting times for surgical patients,average length of stay,patient satisfaction,and anxiety incidence before and after the implementation of the lean model to evaluate its effectiveness.Results After implementing the lean bed resource allocation model,the bed efficiency index increased by 14.29％,and bed turnover rates improved by 3.34％.The average preoperative waiting time for surgical patients decreased by 100％,and the average length of stay reduced by 87.71％.Patient satisfaction increased by 2.4％,while anxiety incidence dropped by 28.1％.Conclusion The implementa-tion of a lean bed resource allocation model can enhance hospital bed efficiency,shorten preoperative waiting times for surgical patients,reduce average length of stay,and improve patient satisfaction.