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 effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

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 construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

Objective To explore the target and mechanism of Fengliao Changweikang in treating irritable bowel syndrome(IBS)based on network pharmacology and molecular docking technology.Methods The effective components of Fengliao Changweikang were screened by data mining,and the drug-target network was constructed to identify the key targets and their pathways related to IBS.The molecular docking verification of the main active ingredients and core target proteins was carried out,and the binding energy was evaluated and the results were visualized.Results Fengliao Changweikang contained 24 potential active ingredients,134 active ingredient targets,and 2353 disease-related targets.After intersecting these,70 potential target points were identified,involving 898 biological processes,96 molecular functions,and 66 cellular components.Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that its mechanism of action in treating IBS may involve regulating key signaling pathways such as cancer pathways,PI3K/Akt signaling pathways,and phospholipase D pathways through interactions with core targets.Molecular docking analysis indicated that the core compounds in Fengliao Changweikang exhibit good binding activity with core receptor proteins.Conclusion Fengliao Changweikang works through multiple signaling pathways and multiple target mechanisms to treat IBS.

Objective To parse the current situation of obstetrics resources in Chinese Public General Hospitals,and explore a new path for the development of obstetric medical service system in public hospitals.Methods Literature search and qualitative interview methods were used to sort out the obstetric resources and services of public general hospitals.Results The obstetrics departments in public general hospitals play an important role in the obstetrics service system,which face more operation pressures and transformation difficulties in the background of low fertility.Public general hospitals can strengthen the inner horizontal integration by multidisciplinary collaboration,and external vertical with medical alliances and obstetric alliances,so as to provide high-quality and continuous obstetric services for regional pregnant women and enhance system resilience.Conclusion Centralized multidisciplinary integration inside the hospitals and alliance with other obstetrics departments outside the hospitals,namely Two"Centralized Development"may be a new path for the high-quality development of obstetrics department in public general hospitals under the background of low fertility rate.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

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.