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.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

OBJECTIVE To explore the prevalence of Ureaplasma urealyticum and Mycoplasma hominis among the patients with chronic cervicitis(CC)and observe their drug resistance to commonly used antibiotics.METHODS A total of 91 patients with CC who were treated in gynecology department of Women and Children's Hospital Affiliated to Ningbo University from Jan.2022 to Jun.2024 were assigned as the CC group,meanwhile,91 healthy women who received physical examination were chosen as the control group.The genital tract secretions were collected from all of the research subjects for the culture of U.urealyticum and M.hominis and drug suscep-tibility testing.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis were com-pared between the two groups.The isolation rates of U.urealyticum and M.hominis were compared among the different age groups of CC patients.The drug susceptibility testing of U.urealyticu m and M.hominis for doxycyc-line(DOX),josamycin(JOS),ofloxacin(OFL),clarithromycin(CLA),erythromycin(ERY),tetracycline(TET),azithromycin(AZI)and pristinamycin(PTN)were observed.RESULTS Totally 75(82.41％)genital tract secretion samples tested positive for Mycoplasma among the 91 samples,37 detected with U.urealyticum,25 were M.hominis,and 13 were U.urealyticum plus M.hominis.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis of the CC group were 40.66％,24.47％and 14.29％,respective-ly,higher than 8.79％,4.40％and 5.49％of the control group(P＜0.05).The total detection rate of U.urealyti-cum,M.hominis and U.urealyticum plus M.hominis was higher among the CC patients aged between 20 and 40 years old than among the CC patients aged more than 40 years old(P＜0.05).The U.urealyticum strains from the positive specimens of the CC patients were highly sensitive to CL A and DOS but were resistant to OFL,CIP and PTN;the M.honinis and U.urealyticum plus M.hominis strains were sensitive to JOS and DOX but were resistant to OFL and CIP.CONCLUSIONS The detection rates of U.urealyticum plus M.hominis are higher a-mong the CC patients than among the normal population.The isolated U.urealyticum and M.hominis strains are highly resistant to quinolones and aminoglycosides.It is necessary for the hospital to empirically choose sensitive antibiotics based on the result of drug susceptibility testing.

OBJECTIVE To explore the prevalence of Ureaplasma urealyticum and Mycoplasma hominis among the patients with chronic cervicitis(CC)and observe their drug resistance to commonly used antibiotics.METHODS A total of 91 patients with CC who were treated in gynecology department of Women and Children's Hospital Affiliated to Ningbo University from Jan.2022 to Jun.2024 were assigned as the CC group,meanwhile,91 healthy women who received physical examination were chosen as the control group.The genital tract secretions were collected from all of the research subjects for the culture of U.urealyticum and M.hominis and drug suscep-tibility testing.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis were com-pared between the two groups.The isolation rates of U.urealyticum and M.hominis were compared among the different age groups of CC patients.The drug susceptibility testing of U.urealyticu m and M.hominis for doxycyc-line(DOX),josamycin(JOS),ofloxacin(OFL),clarithromycin(CLA),erythromycin(ERY),tetracycline(TET),azithromycin(AZI)and pristinamycin(PTN)were observed.RESULTS Totally 75(82.41％)genital tract secretion samples tested positive for Mycoplasma among the 91 samples,37 detected with U.urealyticum,25 were M.hominis,and 13 were U.urealyticum plus M.hominis.The isolation rates of U.urealyticum,M.hominis and U.urealyticum plus M.hominis of the CC group were 40.66％,24.47％and 14.29％,respective-ly,higher than 8.79％,4.40％and 5.49％of the control group(P＜0.05).The total detection rate of U.urealyti-cum,M.hominis and U.urealyticum plus M.hominis was higher among the CC patients aged between 20 and 40 years old than among the CC patients aged more than 40 years old(P＜0.05).The U.urealyticum strains from the positive specimens of the CC patients were highly sensitive to CL A and DOS but were resistant to OFL,CIP and PTN;the M.honinis and U.urealyticum plus M.hominis strains were sensitive to JOS and DOX but were resistant to OFL and CIP.CONCLUSIONS The detection rates of U.urealyticum plus M.hominis are higher a-mong the CC patients than among the normal population.The isolated U.urealyticum and M.hominis strains are highly resistant to quinolones and aminoglycosides.It is necessary for the hospital to empirically choose sensitive antibiotics based on the result of drug susceptibility testing.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear. OBJECTIVE:To investigate the involvement of myocytes,fascia cells,and endothelial cells in the process of heterotopic ossification in skeletal muscle and to observe the cell origin of heterotopic ossification in skeletal muscle induced by bone morphogenetic protein 4. METHODS:Both C2C12 cells and the myotubes formed by the C2C12 cells in the induction medium were cultured,and 500 ng/mL bone morphogenetic protein 4 was added to the medium respectively,and whether the C2C12 cells and myotubes continued to proliferate within 10 days under the treatment were observed under a microscope.Myogenic cells(L6,derived from rats)and fibroblast-derived cells(derived from human)were co-cultured.After treatment with 500 ng/mL bone morphogenetic protein 4 and 10 ng/mL transforming growth factor-β,osteogenic and chondrogenic differentiation potential within 21 days were observed using Safranine O staining and Alcian blue staining.Using transgenic animal FVB/N-TgN(TIE2-LacZ)182Sato mice,15 μL of adeno-associated virus-bone morphogenetic protein 4(5×1010 PFU/mL)were implanted in the thigh muscle space of genetic mice for 10 and 14 days.X-gal staining was used to observe the formation of new blood vessel endothelium in the differentiated bone. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein 4 caused myotube breakdown and increased C2C12 cell proliferation.Compared with other groups,the pure fibroblast-derived cell group had a higher area of positive alcian blue and safarin O staining(P<0.05)and a lower area of alkaline phosphatase staining(P<0.05),while the pure L6 group had a bigger area of alkaline phosphatase staining(P<0.05)but a smaller area of positive alcian blue and safarin O staining(P<0.05).(2)Transplantation of adeno-associated virus-bone morphogenetic protein 4-adsorbed gelatin sponge into FVB/N-TgN(TIE2-LacZ)182Sato mice resulted in heterotopic ossification.(3)X-gal staining results demonstrated that there was no obvious staining in chondrocytes and differentiated bones and Tie2+ endothelial cells did not participate in the formation of the alienated bone.(4)These findings verify that fibroblasts are the primary source of osteoblasts during the adeno-associated virus-bone morphogenetic protein 4-induced ectopic endochondral ossification in skeletal muscle,but myogenic cells are the main source of osteoblasts.Tie2+ endothelial cells might not be the cell source for cartilage and bone.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.