Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective:To analyze the result data of the first competition of medical-industrial integration innovation for transformation of the Pathological Equipment Branch of China Association of Medical Equipment,so as to explore the directions of medical-industrial integration and transformation innovation in the field of pathology.Methods:The data of the participated projects of the first competition of medical-industrial integration innovation for transformation in 2024,which was held by the Pathological Equipment Branch of China Association of Medical Equipment,were collected,and these data were divided into equipment category,and the category of reagents and consumables according to their declaration content.The data of the results of preliminary and final competition,award information,transformation number and other data of the two categories of participated projects were analyzed,and the scoring differences between the judges who were expert,and the judges from enterprise were compared.Results:This competition received 21 projects,which included 15 projects of equipment category,and 6 projects of the category of reagents and consumables.In 21 projects,there were 10 projects wined award,which included 7 projects of equipment category,and 3 projects of the category of reagents and consumables.There was not statistically significant difference in the results between equipment category and the category of reagents and consumables in preliminary and final competitions(P>0.05).There was not significant difference in the ratio between equipment category(46.7%)and the category of reagents and consumables(50%)(P>0.05).The results of preliminary and final competitions of the projects in equipment category were respectively(70.64±3.48)and(76.49±2.34),and the difference was significant(t=5.403,P<0.05).There was not significant difference in the category of reagents and consumables between preliminary and final competitions(P>0.05).In 15 projects of equipment category,6 projects obtained the intention of transformation from enterprises.In 6 projects of the category of reagents and consumables,3 projects obtained the intention of transformation from enterprises.The score of judges who were expert,and the score of judges from enterprise were respectively(68.90±4.76)and(71.90±4.38)for the results of preliminary competition,and the difference was significant(t=2.121,P<0.05).Conclusion:The competition of medical-industrial integration innovation for transformation has successfully built a bridge between pathological patent and enterprises,which can effectively promote the transformation of pathology-related patents,and promote a deep integration between medicine and engineering.It also can accelerate the application of innovational technique in pathological field,and the connection between product's development stage and related enterprises,and can construct a harmonious development environment for transformation and innovation of medical-industrial integration.

Objective:To investigate the application value of 68Ga-Pentixafor PET/CT targeting CXC subfamily receptor 4 (CXCR4) in the subtyping and precise localization of primary aldosteronism (PA). Methods:Thirty-three patients with PA confirmed by clinical examination and undergoing 68Ga-Pentixafor PET/CT and adrenal vein sampling (AVS) in the Second Xiangya Hospital between July 1st 2022 and July 1st 2023 were prospectively enrolled (24 males, 9 females, age (49.6±10.3) years). Patients with a dominant side identified by PET/CT or AVS underwent unilateral adrenalectomy, while those without a dominant side received medical treatment. According to the standard of PA surgical outcome (PASO), patients underwent surgery were divided into unilateral PA (UPA) and bilateral PA (BPA) based on the pathological and follow-up results. Those who received medical treatment were BPA. The diagnostic efficacy of 68Ga-Pentixafor PET/CT for UPA was calculated. The ROC curve was constructed to analyze the accuracy and optimal threshold of SUV max, the ratio of lesion SUV max to contralateral adrenal tissue SUV mean (LCR), and the ratio of lesion SUV max to liver SUV mean (LLR) in the diagnosis of PA subtype. The correlation between the quantitative parameters and the clinical features and lesion width of the patients was evaluated by Spearman rank correlation analysis. The differences of LCR and LLR between different efficacy groups were compared by the independent-sample t test. Results:A total of 20 patients underwent unilateral adrenalectomy. Nineteen patients were finally diagnosed with UPA and 14 with BPA. The agreement rate of PET/CT and AVS was 81.8%(27/33), and both methods independently detected UPA that was negative in the other examination. The sensitivity, specificity, and accuracy of 68Ga-Pentixafor PET/CT visual diagnosis of UPA were 18/19, 14/14, and 97.0%(32/33), respectively. ROC curve showed that the AUC of LLR for subtype diagnosis was 0.944, with the optimal threshold of 3.1. SUV max, LCR, and LLR were positively correlated with aldosterone concentration ( rs values: 0.35, 0.47, and 0.36, all P<0.05) and lesion width ( rs values: 0.43, 0.49, and 0.58, all P<0.05). The LCR (3.9±2.2 vs 1.6±0.3; t=2.00, P=0.041) and LLR( 8.7±4.1 vs 4.2±1.3; t=2.06, P=0.045) of the dominant side lesions in patients who achieved complete biochemical and clinical cure were higher than those in patients with partial improvement. Conclusions:68Ga-Pentixafor PET/CT imaging can be used in the diagnosis and precise localization of PA subtype. It also can detect patients with PA which can be surgically cured but not detected by AVS, and the quantitative analysis may be valuable for prognosis prediction.

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

Serotonin syndrome (SS), also known as serotonin toxicity, is a rare but life-threatening drug reaction syndrome. This case involves a 17-year-old female patient who developed tremors, fatigue, and tachycardia after taking fluoxetine combined with bupropion and tandospirone for five days. SS was highly suspected, and her symptoms improved following treatment targeted at serotonin syndrome. This case is reported to raise awareness among clinicians about the potential adverse reactions of drug combinations, the importance of early identification of SS symptoms, and precautions when prescribing combined medications to avoid serious consequences.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.

Objective This study aimed to evaluate the clinical effect of hyaluronic acid(HA)scaffold combined with adipose-derived stem cells(ADSCs)in chronic wound healing of lower limbs and explore its applica-tion potential in promoting chronic wound healing.Methods A total of 50 patients were included in this study.They were divided into study and control groups according to the random number table method.There were 25 cases in each of the two groups of patients.HA and ADSCs were mixed in a 1:1 ratio and evenly injected into the wound base and the subcutaneous tissue around the wound at a rate of 0.1 ml/cm3.In the control group,ADSCs were only injected into the wound base and subcutaneous tissue around the wound.The infection rate,treatment satisfaction,wound healing rate,visual analogue score(VAS),and wound quantitative score were compared between the two groups at 7 days,14 days,and 28 days.Results The infection rate in the study group was lower than that in the control group,and the difference was statistically significant(P<0.05).Moreover,at 14 days and 28 days after treatment,the wound healing rate in the study group was higher than that in the control group,and the difference was statistically significant(P<0.05).On the 7th,14th,and 28th days after treatment,the VAS scores and the wound quantitative scores were lower than those in the control group,and the difference was statisti-cally significant(P<0.05).Furthermore,the treatment satisfaction rate in the research group(92％)was higher than that in the control group(80％).Conclusion HA scaffold combined with ADSCs could promote the healing of chronic wounds in lower limbs,reduce infection rate,and relieve wound pain,which provides a new idea for the treatment of chronic wounds.

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

Objective This study aimed to evaluate the clinical effect of hyaluronic acid(HA)scaffold combined with adipose-derived stem cells(ADSCs)in chronic wound healing of lower limbs and explore its applica-tion potential in promoting chronic wound healing.Methods A total of 50 patients were included in this study.They were divided into study and control groups according to the random number table method.There were 25 cases in each of the two groups of patients.HA and ADSCs were mixed in a 1:1 ratio and evenly injected into the wound base and the subcutaneous tissue around the wound at a rate of 0.1 ml/cm3.In the control group,ADSCs were only injected into the wound base and subcutaneous tissue around the wound.The infection rate,treatment satisfaction,wound healing rate,visual analogue score(VAS),and wound quantitative score were compared between the two groups at 7 days,14 days,and 28 days.Results The infection rate in the study group was lower than that in the control group,and the difference was statistically significant(P<0.05).Moreover,at 14 days and 28 days after treatment,the wound healing rate in the study group was higher than that in the control group,and the difference was statistically significant(P<0.05).On the 7th,14th,and 28th days after treatment,the VAS scores and the wound quantitative scores were lower than those in the control group,and the difference was statisti-cally significant(P<0.05).Furthermore,the treatment satisfaction rate in the research group(92％)was higher than that in the control group(80％).Conclusion HA scaffold combined with ADSCs could promote the healing of chronic wounds in lower limbs,reduce infection rate,and relieve wound pain,which provides a new idea for the treatment of chronic wounds.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.