Autosomal dominant polycystic kidney disease （ADPKD） is a systemic hereditary renal disorder and can affect multiple organs， and congenital hepatic fibrosis is one of the manifestations of liver involvement and is an important complication of ADPKD. Symptomatic management is currently the main treatment method for this disease， and disease-specific drugs such as tolvaptan have limited indications and cannot correct the underlying genetic defect. This article reports a case of ADPKD with congenital hepatic fibrosis， and sirolimus was identified as the individualized treatment regimen based on peripheral blood functional genomic analysis and drug sensitivity prediction platform. The patient achieved significant improvements in symptoms and quality of life after treatment， with a stable kidney volume. This case shows that functional genomics has a potential value in guiding individualized treatment of rare genetic disorders， which provides new treatment ideas and practice paths for similar patients.

Objective The aim is to understand the common scenarios of non-medical use of prescription opioids(NMUPO)and analyze the potential facilitating and hindering factors in the regulatory process of NMUPO from the perspective of healthcare professionals.Methods Healthcare professionals in local hospitals were surveyed through a two-stage purposive sampling from June to August 2022 in Ningbo,China.The survey was conducted using a semi-structured questionnaire on topics,and thematic analysis were used to identify and summarise key themes and patterns.Results A total of 75 participants were included,the average age was(43.9±7.2)years,and 54(72.0%)were male.The most common NMUPO scenarios involved middle-aged males pretending acute severe pain to obtain injectable opioids.The facilitating and hindering factors related to the regulation of NMUPO can be categorized into three types:institutional governance,technical support,and individual behaviors.At the institutional level,facilitating factors included strict national prescribing policies and local"narcotic drug card"systems,while barriers comprised incomplete lists of controlled substances.At the technological support level,facilitating factors included the establishment of regional health information platforms,while barriers included the lack of standardized prescription guidelines and diagnostic decision-support tools.At the individual level,facilitating factors included the public's cautious attitude toward drug misuse,while barriers included strained doctor-patient relationships.Conclusion China still faces significant challenges in addressing NMUPO and urgently needs to improve the existing regulatory system.It is recommended that reforms be carried out in areas such as pharmaceutical control mechanisms,drug treatment and rehabilitation services,preventive health education activities,and the optimized use of health information systems.

Objective:To explore the application of bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS) combined with knowledge point auction-based learning in the internship teaching of pediatric general surgery nursing students.Methods:Ninety nursing students completing internships in the General Surgery Department of Children's Hospital, Zhejiang University School of Medicine from July 2022 to April 2024 were selected as the research subjects. According to the order of admission, they were divided into control group (July 2022 to May 2023) and experimental group (June 2023 to April 2024), with 45 students in each group. The control group received conventional teaching, while the experimental group received BOPPPS teaching combined with knowledge point auction-based learning. Theoretical and practical training assessment scores were compared between the two groups. Additionally, a survey on the degree of satisfaction with the teaching was administered upon internship completion . Data were analyzed using t-tests with SPSS 26.0. Results:The theoretical scores of nursing students in the experimental group were higher than those in the control group, and the difference was statistically significant; The performance of the experimental group's nursing students in practical training assessment was higher than that of the control group [peripheral venous puncture catheterization: (27.62±2.10) vs. (22.41±3.80)]; Gastrointestinal decompression technique: (22.82±1.70) vs. (18.21±2.91); Rescue of anaphylactic shock: (16.52±3.13) vs. (21.32±2.41); There was a statistically significant difference in the evaluation of teacher guidance ability between the two groups of nursing students in terms of intestinal fistula nursing (14.11±2.70) vs. (17.90±1.93). However, there was no statistically significant difference in the satisfaction score of the experimental group nursing students in other aspects of teaching compared to the control group, and the difference was statistically significant.Conclusions:BOPPPS combined with knowledge point auction-based learning improves knowledge mastery in clinical teaching for pediatric general surgery interns, enhance operational confidence, and is readily accepted by students.

Objective:To explore the mechanism of astaxanthin improving renal damage in diabetic mice by regulating the PI3K/Akt signaling pathway.Methods:C57BL/6J adult male mice (8 weeks, 22-24 g) were provided by Nanjing Junke Biological Co.,Ltd. The mice were divided into control group (mice raised under normal conditions and given phosphate buffered saline injection, n=15), model group (DN mouse model established as mentioned above, n=15), and astaxanthin group (on the basis of model mice,10 mg/kg body weight dose of astaxanthin was given, n=15). The serum urea nitrogen, serum creatinine and 24 h urine protein levels of mice were detected by biochemical kits. The levels of serum inflammatory factors in mice were detected by ELISA. Mesangial matrix expansion and fibrosis in mice were observed by renal histological analysis. Glomerular podocytes were analyzed by TUNEL detection and immunohistochemical staining. Nephrin and CD2AP expression were analyzed by Western blot.The expression of PI3K/Akt signaling pathway was analyzed by Western blot. Results:The levels of serum urea nitrogen, serum creatinine and 24h urinary protein in model group were higher than those in control group ( P<0.05), but the levels of serum urea nitrogen, serum creatinine and 24h urinary protein in astaxanthin group were lower than those in model group ( P<0.05). The serum levels of TNF-α,1L-1β and 1L-6 in model group were higher than those in control group ( P<0.05), while the levels of TNF-α,1L-1β and 1L-6 in astaxanthin group were lower than those in model group ( P<0.05). Compared with the control group, the model group mainly showed different degrees of pancreatic islet lesions and vacuolar degeneration under light microscope ( P<0.05). HE staining showed glomerular sclerosis and dilatation, capillary lumen shrinkage, diffuse mesangial matrix dilatation, and peripheral capillary thickening and hardening ( P<0.05). PAS staining showed an increase in PAS-positive substances (purple plaques) in the model group of mice ( P<0.05), indicating glycogen accumulation in diabetic glomeruli. Masson staining showed accumulation of type Ⅳ collagen and increased fibrosis (blue stained area) in the kidney of the model group ( P<0.05). Astaxanthin treatment can significantly improve these diabetic induced histopathological changes ( P<0.05). Compared with control group,mesangial matrix expansion and fibrosis were increased in model group ( P<0.05), and decreased in astaxanthin group ( P<0.05). Compared with the control group, the apoptosis rate of podocyte in model group was increased ( P<0.05) ,while that in astaxanthin group was decreased ( P<0.05). The number of WT-1 positive podocytes in model group was lower than that in model group ( P<0.05), and the number of WT-1 positive podocytes in astaxanthin group was higher than that in model group ( P<0.05). Compared with the control group, Nephrin and CD2AP proteins in the model group were decreased ( P<0.05), and the expressions of Nephrin and CD2AP proteins in astaxanthin group were increased ( P<0.05). The protein expressions of p85, p-Akt Ser473 and P-mtor Ser2448 in model group were increased compared with those in control group ( P<0.05), while the protein expressions of p85, P-Akt Ser473 and P-mtor Ser2448 in astaxanthin group were decreased compared with those in model group ( P<0.05) . Conclusion:Astaxanthin significantly improves kidney damage in diabetic mice by regulating the PI3K/Akt signaling pathway,which manifests as inhibiting renal cell lesions and reducing inflammation.

Objective The aim is to understand the common scenarios of non-medical use of prescription opioids(NMUPO)and analyze the potential facilitating and hindering factors in the regulatory process of NMUPO from the perspective of healthcare professionals.Methods Healthcare professionals in local hospitals were surveyed through a two-stage purposive sampling from June to August 2022 in Ningbo,China.The survey was conducted using a semi-structured questionnaire on topics,and thematic analysis were used to identify and summarise key themes and patterns.Results A total of 75 participants were included,the average age was(43.9±7.2)years,and 54(72.0%)were male.The most common NMUPO scenarios involved middle-aged males pretending acute severe pain to obtain injectable opioids.The facilitating and hindering factors related to the regulation of NMUPO can be categorized into three types:institutional governance,technical support,and individual behaviors.At the institutional level,facilitating factors included strict national prescribing policies and local"narcotic drug card"systems,while barriers comprised incomplete lists of controlled substances.At the technological support level,facilitating factors included the establishment of regional health information platforms,while barriers included the lack of standardized prescription guidelines and diagnostic decision-support tools.At the individual level,facilitating factors included the public's cautious attitude toward drug misuse,while barriers included strained doctor-patient relationships.Conclusion China still faces significant challenges in addressing NMUPO and urgently needs to improve the existing regulatory system.It is recommended that reforms be carried out in areas such as pharmaceutical control mechanisms,drug treatment and rehabilitation services,preventive health education activities,and the optimized use of health information systems.

Objective:To analyze the clinical features and prognosis of patients with lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM) transformed into diffuse large B-cell lymphoma (DLBCL) .Methods:This study retrospectively analyzed the clinical data of five patients with LPL/WM transformed to DLBCL diagnosed and treated at a multicenter hospital in Hunan Province from December 2020 to April 2023. Clinical manifestations, treatment regimens, and therapeutic efficacy before and after the transformation were compared.Results:Of the five patients, four were male and one was female, with a median age of 64.0 (57.0–80.0) years, all of whom had abnormally increased β 2-microglobulin levels at diagnosis, and two were combined with increased lactate dehydrogenase levels. The MYD88 L265P mutation was detected in 4 patients, whereas 1 carried the FAT1 and NOTCH1 mutations, and none demonstrated CXCR4 mutations. Three patients were negative for the TP53 mutation, and two were not tested. Before transformation, three patients were treated with Bruton tyrosine kinase inhibitor therapy, and one patient was treated with the bendamustine plus rituximab regimen. All patients eventually transformed into non-growth center-derived DLBCL, with a median time to conversion of 11.8 (4.0–19.0) months, and most of them presented with weight loss, lymph node enlargement, splenomegaly, and extranodal involvement. Posttransformation, the patients were mainly treated with the rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen, with an optimal outcome of partial remission. Disease progression occurred in 4 of the patients, with a median overall survival of 16.8 (10.0–26.0) months. Conclusion:Transformation from LPL/WM to DLBCL is rare. Patients should remain highly vigilant for transformation if they develop rapidly enlarging lymph nodes and/or newly involved lymph nodes, worsening systemic symptoms, and declining body mass. R-CHOP regimen may induce a partial response in some cases; however, the overall prognosis remains poor.

Objective:To explore the application of bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS) combined with knowledge point auction-based learning in the internship teaching of pediatric general surgery nursing students.Methods:Ninety nursing students completing internships in the General Surgery Department of Children's Hospital, Zhejiang University School of Medicine from July 2022 to April 2024 were selected as the research subjects. According to the order of admission, they were divided into control group (July 2022 to May 2023) and experimental group (June 2023 to April 2024), with 45 students in each group. The control group received conventional teaching, while the experimental group received BOPPPS teaching combined with knowledge point auction-based learning. Theoretical and practical training assessment scores were compared between the two groups. Additionally, a survey on the degree of satisfaction with the teaching was administered upon internship completion . Data were analyzed using t-tests with SPSS 26.0. Results:The theoretical scores of nursing students in the experimental group were higher than those in the control group, and the difference was statistically significant; The performance of the experimental group's nursing students in practical training assessment was higher than that of the control group [peripheral venous puncture catheterization: (27.62±2.10) vs. (22.41±3.80)]; Gastrointestinal decompression technique: (22.82±1.70) vs. (18.21±2.91); Rescue of anaphylactic shock: (16.52±3.13) vs. (21.32±2.41); There was a statistically significant difference in the evaluation of teacher guidance ability between the two groups of nursing students in terms of intestinal fistula nursing (14.11±2.70) vs. (17.90±1.93). However, there was no statistically significant difference in the satisfaction score of the experimental group nursing students in other aspects of teaching compared to the control group, and the difference was statistically significant.Conclusions:BOPPPS combined with knowledge point auction-based learning improves knowledge mastery in clinical teaching for pediatric general surgery interns, enhance operational confidence, and is readily accepted by students.

Objective:To explore the mechanism of astaxanthin improving renal damage in diabetic mice by regulating the PI3K/Akt signaling pathway.Methods:C57BL/6J adult male mice (8 weeks, 22-24 g) were provided by Nanjing Junke Biological Co.,Ltd. The mice were divided into control group (mice raised under normal conditions and given phosphate buffered saline injection, n=15), model group (DN mouse model established as mentioned above, n=15), and astaxanthin group (on the basis of model mice,10 mg/kg body weight dose of astaxanthin was given, n=15). The serum urea nitrogen, serum creatinine and 24 h urine protein levels of mice were detected by biochemical kits. The levels of serum inflammatory factors in mice were detected by ELISA. Mesangial matrix expansion and fibrosis in mice were observed by renal histological analysis. Glomerular podocytes were analyzed by TUNEL detection and immunohistochemical staining. Nephrin and CD2AP expression were analyzed by Western blot.The expression of PI3K/Akt signaling pathway was analyzed by Western blot. Results:The levels of serum urea nitrogen, serum creatinine and 24h urinary protein in model group were higher than those in control group ( P<0.05), but the levels of serum urea nitrogen, serum creatinine and 24h urinary protein in astaxanthin group were lower than those in model group ( P<0.05). The serum levels of TNF-α,1L-1β and 1L-6 in model group were higher than those in control group ( P<0.05), while the levels of TNF-α,1L-1β and 1L-6 in astaxanthin group were lower than those in model group ( P<0.05). Compared with the control group, the model group mainly showed different degrees of pancreatic islet lesions and vacuolar degeneration under light microscope ( P<0.05). HE staining showed glomerular sclerosis and dilatation, capillary lumen shrinkage, diffuse mesangial matrix dilatation, and peripheral capillary thickening and hardening ( P<0.05). PAS staining showed an increase in PAS-positive substances (purple plaques) in the model group of mice ( P<0.05), indicating glycogen accumulation in diabetic glomeruli. Masson staining showed accumulation of type Ⅳ collagen and increased fibrosis (blue stained area) in the kidney of the model group ( P<0.05). Astaxanthin treatment can significantly improve these diabetic induced histopathological changes ( P<0.05). Compared with control group,mesangial matrix expansion and fibrosis were increased in model group ( P<0.05), and decreased in astaxanthin group ( P<0.05). Compared with the control group, the apoptosis rate of podocyte in model group was increased ( P<0.05) ,while that in astaxanthin group was decreased ( P<0.05). The number of WT-1 positive podocytes in model group was lower than that in model group ( P<0.05), and the number of WT-1 positive podocytes in astaxanthin group was higher than that in model group ( P<0.05). Compared with the control group, Nephrin and CD2AP proteins in the model group were decreased ( P<0.05), and the expressions of Nephrin and CD2AP proteins in astaxanthin group were increased ( P<0.05). The protein expressions of p85, p-Akt Ser473 and P-mtor Ser2448 in model group were increased compared with those in control group ( P<0.05), while the protein expressions of p85, P-Akt Ser473 and P-mtor Ser2448 in astaxanthin group were decreased compared with those in model group ( P<0.05) . Conclusion:Astaxanthin significantly improves kidney damage in diabetic mice by regulating the PI3K/Akt signaling pathway,which manifests as inhibiting renal cell lesions and reducing inflammation.

Objective:To analyze the clinical features and prognosis of patients with lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM) transformed into diffuse large B-cell lymphoma (DLBCL) .Methods:This study retrospectively analyzed the clinical data of five patients with LPL/WM transformed to DLBCL diagnosed and treated at a multicenter hospital in Hunan Province from December 2020 to April 2023. Clinical manifestations, treatment regimens, and therapeutic efficacy before and after the transformation were compared.Results:Of the five patients, four were male and one was female, with a median age of 64.0 (57.0–80.0) years, all of whom had abnormally increased β 2-microglobulin levels at diagnosis, and two were combined with increased lactate dehydrogenase levels. The MYD88 L265P mutation was detected in 4 patients, whereas 1 carried the FAT1 and NOTCH1 mutations, and none demonstrated CXCR4 mutations. Three patients were negative for the TP53 mutation, and two were not tested. Before transformation, three patients were treated with Bruton tyrosine kinase inhibitor therapy, and one patient was treated with the bendamustine plus rituximab regimen. All patients eventually transformed into non-growth center-derived DLBCL, with a median time to conversion of 11.8 (4.0–19.0) months, and most of them presented with weight loss, lymph node enlargement, splenomegaly, and extranodal involvement. Posttransformation, the patients were mainly treated with the rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen, with an optimal outcome of partial remission. Disease progression occurred in 4 of the patients, with a median overall survival of 16.8 (10.0–26.0) months. Conclusion:Transformation from LPL/WM to DLBCL is rare. Patients should remain highly vigilant for transformation if they develop rapidly enlarging lymph nodes and/or newly involved lymph nodes, worsening systemic symptoms, and declining body mass. R-CHOP regimen may induce a partial response in some cases; however, the overall prognosis remains poor.

Objective:To apply digital analysis to quantify hyperechogenicity of substantia nigra, and explore its clinical value for diagnosis of Parkinson′s disease (PD).Methods:The cross-sectional study included 652 PD patients (PD group) and 99 healthy controls (healthy control group) from November 2017 to October 2020 in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. All subjects underwent transcranial sonography. The diagnostic accuracy of substantia nigra hyperechogenicity using digital analysis was compared with that in a manual measurement in PD. Furthermore, the receiver operating characteristic (ROC) curve analysis was applied to explore its diagnosis value in PD.Results:There were 482 subjects including 400 in the PD group and 82 in the healthy control group, whose quantified results of substantia nigra hyperechogenicity could be used for analysis. The ROC analysis showed that the area under the curve of the quantified larger substantia nigra hyperechoic region detection for diagnosing PD was 0.858 (95% CI 0.805-0.910), the sensitivity was 87.8%, and the specificity was 73.2%, consistent with that of doctors (area under the curve: 0.884). Further more, among these PD patients, there was no correlation between larger substantia nigra hyperechogenicity and age, age of onset, course of disease, non-motor symptoms, and motor symptoms (all P>0.05). Conclusions:Digital analysis was used to quantify the changes in substantia nigra hyperechogenicity in this seudy. The results showed that diagnostic accuracy for PD based on digital analysis was consistent with that of experienced clinicians.