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 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 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 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 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 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 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 investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.