Background and purpose:For few of early-stage breast cancers who are undiagnosed by core needle biopsy,the delayed diagnosis rate of intraoperative rapid frozen section pathological examination is unclear.The purpose of this retrospective cohort study was to investigate the clinical application value of frozen sections in this situation.Methods:This study reviewed data of 876 breast cancer patients that were undiagnosed by core needle biopsy in Fudan University Shanghai Cancer Center from May 1,2006 to December 31,2019.Clinical characteristics and image data and pathological data of patients were collected.The correlation between clinical features and delayed diagnosis rate(DDR)of frozen section was explored using logistic regression analysis,then a nomogram was constructed to predict the probability of delayed diagnosis.This study was approved by Ethics Committee of Fudan University Shanghai Cancer Center(No.:050432-4-2108*).Results:A total of 876 patients met the inclusion standards.The intraoperative diagnosis rate of frozen section for breast cancers that were undiagnosed by core needle biopsy was 67.7%,and the DDR was 32.3%.In multivariate analysis,papillary lesion[odds ratio(OR)=4.251,95%CI:2.804-6.492;P＜0.001)and sclerosing adenosis(OR=3.727;95%CI:1.897-7.376;P＜0.001)accompanied by atypical epithelial hyperplasia on core needle biopsy(CNB)were positive correlation factors of delayed diagnosis,while clustered microcalcifications on mammography(OR=0.345;95%CI:0.216-0.543;P＜0.001)and ultrasonic category 4C-5 according to Breast Imaging Reporting and Data System(BI-RADS)(OR=0.250;95%CI:0.081-0.777;P=0.016)were positive correlation factors of intraoperative diagnosis.The nomogram constructed by these factors could better predict the delayed diagnosis rate of frozen section and screen out low delayed diagnosis population.Conclusion:Frozen section has a certain delayed diagnosis rate for breast cancer that is not clearly diagnosed by core needle biopsy.The method of model prediction can effectively eliminate the delayed diagnosis cases and avoid some unnecessary frozen sections.

Background and purpose:For few of early-stage breast cancers who are undiagnosed by core needle biopsy,the delayed diagnosis rate of intraoperative rapid frozen section pathological examination is unclear.The purpose of this retrospective cohort study was to investigate the clinical application value of frozen sections in this situation.Methods:This study reviewed data of 876 breast cancer patients that were undiagnosed by core needle biopsy in Fudan University Shanghai Cancer Center from May 1,2006 to December 31,2019.Clinical characteristics and image data and pathological data of patients were collected.The correlation between clinical features and delayed diagnosis rate(DDR)of frozen section was explored using logistic regression analysis,then a nomogram was constructed to predict the probability of delayed diagnosis.This study was approved by Ethics Committee of Fudan University Shanghai Cancer Center(No.:050432-4-2108*).Results:A total of 876 patients met the inclusion standards.The intraoperative diagnosis rate of frozen section for breast cancers that were undiagnosed by core needle biopsy was 67.7%,and the DDR was 32.3%.In multivariate analysis,papillary lesion[odds ratio(OR)=4.251,95%CI:2.804-6.492;P＜0.001)and sclerosing adenosis(OR=3.727;95%CI:1.897-7.376;P＜0.001)accompanied by atypical epithelial hyperplasia on core needle biopsy(CNB)were positive correlation factors of delayed diagnosis,while clustered microcalcifications on mammography(OR=0.345;95%CI:0.216-0.543;P＜0.001)and ultrasonic category 4C-5 according to Breast Imaging Reporting and Data System(BI-RADS)(OR=0.250;95%CI:0.081-0.777;P=0.016)were positive correlation factors of intraoperative diagnosis.The nomogram constructed by these factors could better predict the delayed diagnosis rate of frozen section and screen out low delayed diagnosis population.Conclusion:Frozen section has a certain delayed diagnosis rate for breast cancer that is not clearly diagnosed by core needle biopsy.The method of model prediction can effectively eliminate the delayed diagnosis cases and avoid some unnecessary frozen sections.

BACKGROUND:The study of deer antler stem cells and exosomes to promote the repair of acute skin injuries has received increasing attention in recent years,but the effect and mechanism of exosomes composite hydrogel to promote the repair of burn wounds are still unclear.OBJECTIVE:To investigate the effect of deer antler stem cell exosome composite hydrogel on the healing speed and quality of rat deep third-degree burn wound and its mechanism of action.METHODS:Deer antler stem cell exosomes and bone marrow mesenchymal stem cell exosomes were extracted and compounded with Pluronic F-127 to prepare a temperature-sensitive hydrogel.A constant temperature and pressure burn apparatus was used to prepare a rat model of deep third-degree burn.The drug was administered to four groups:deer antler stem cell exosome composite hydrogel group,bone marrow mesenchymal stem cell exosome composite hydrogel group,human epidermal growth factor gel group,and the control group.The healing of burned rats was observed and the wound healing rate was calculated.At 28 days after burn,hematoxylin-eosin staining was used to observe the generation of skin accessory structures in the healing tissues.Masson staining was used to analyze the accumulation of collagen in the healing tissues.Immunohistochemistry was used to examine the angiogenesis and nflammatory response in the healing tissues.qRT-PCR was used to examine the expression level of mRNA of the wound healing-related genes in the healing tissues.RESULTS AND CONCLUSION:(1)Deer antler stem cell exosome composite hydrogel can significantly promote the healing rate of deep burn wounds in rats,and improve the quality of wound healing by promoting the regeneration of skin collateral structures,increasing the dermal thickness and enhancing the accumulation of collagen.(2)The number of myofibroblasts in the wound healing tissues of deer antler stem cell exosome composite hydrogel group was significantly reduced,and the number of neovascularization and M2 macrophages was significantly increased.(3)The mRNA levels of transforming growth factor β3 and type Ⅲ collagen in the wound healing tissue of deer antler stem cell exosome composite hydrogel group were significantly higher than those of the blank group,and the mRNA levels of transforming growth factor β1,matrix metalloproteinase 3,and type Ⅰ collagen were significantly lower than those of the blank group,and there was no significant difference between the bone marrow-derived mesenchymal stem cell exosome composite hydrogel group and the human epidermal growth factor gel group.In conclusion,deer antler stem cell exosome composite hydrogel can promote the healing speed and the quality of healing of deep burned wounds in rats,which may be achieved by inhibiting fibroblastogenesis,promoting angiogenesis,macrophage M2 polarization,and regulating the expression of genes for collagen production/degradation.

BACKGROUND:The study of deer antler stem cells and exosomes to promote the repair of acute skin injuries has received increasing attention in recent years,but the effect and mechanism of exosomes composite hydrogel to promote the repair of burn wounds are still unclear.OBJECTIVE:To investigate the effect of deer antler stem cell exosome composite hydrogel on the healing speed and quality of rat deep third-degree burn wound and its mechanism of action.METHODS:Deer antler stem cell exosomes and bone marrow mesenchymal stem cell exosomes were extracted and compounded with Pluronic F-127 to prepare a temperature-sensitive hydrogel.A constant temperature and pressure burn apparatus was used to prepare a rat model of deep third-degree burn.The drug was administered to four groups:deer antler stem cell exosome composite hydrogel group,bone marrow mesenchymal stem cell exosome composite hydrogel group,human epidermal growth factor gel group,and the control group.The healing of burned rats was observed and the wound healing rate was calculated.At 28 days after burn,hematoxylin-eosin staining was used to observe the generation of skin accessory structures in the healing tissues.Masson staining was used to analyze the accumulation of collagen in the healing tissues.Immunohistochemistry was used to examine the angiogenesis and nflammatory response in the healing tissues.qRT-PCR was used to examine the expression level of mRNA of the wound healing-related genes in the healing tissues.RESULTS AND CONCLUSION:(1)Deer antler stem cell exosome composite hydrogel can significantly promote the healing rate of deep burn wounds in rats,and improve the quality of wound healing by promoting the regeneration of skin collateral structures,increasing the dermal thickness and enhancing the accumulation of collagen.(2)The number of myofibroblasts in the wound healing tissues of deer antler stem cell exosome composite hydrogel group was significantly reduced,and the number of neovascularization and M2 macrophages was significantly increased.(3)The mRNA levels of transforming growth factor β3 and type Ⅲ collagen in the wound healing tissue of deer antler stem cell exosome composite hydrogel group were significantly higher than those of the blank group,and the mRNA levels of transforming growth factor β1,matrix metalloproteinase 3,and type Ⅰ collagen were significantly lower than those of the blank group,and there was no significant difference between the bone marrow-derived mesenchymal stem cell exosome composite hydrogel group and the human epidermal growth factor gel group.In conclusion,deer antler stem cell exosome composite hydrogel can promote the healing speed and the quality of healing of deep burned wounds in rats,which may be achieved by inhibiting fibroblastogenesis,promoting angiogenesis,macrophage M2 polarization,and regulating the expression of genes for collagen production/degradation.

Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.

OBJECTIVE To systematically evaluate the efficacy of dydrogesterone combined with estradiol valerate for the prevention of intrauterine adhesion （IUA） and prognosis improvement after induced abortion. METHODS Retrieved from CNKI， Wanfang Data， VIP， CBM， PubMed， Embase and the Cochrane Library， randomized controlled trial （RCT） about conventional treatment combined with dydrogesterone and estradiol valerate （trial group） versus conventional treatment （control group） for the prevention of IUA in patients after induced abortion were collected from the inception to Dec. 2024. After screening the literature， extracting data and evaluating the quality of literature， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 RCTs were included， involving 1 109 patients. Meta-analysis showed that the postoperative incidence of IUA [RR＝0.30， 95%CI （0.22， 0.41）， P＜0.000 01]， postoperative vaginal bleeding time [MD＝－1.69， 95%CI （－2.05， －1.32）， P＜0.000 01]， postoperative vaginal bleeding volume [MD＝－10.78， 95%CI （－12.19， －9.37）， P＜0.000 01]， postoperative menstrual resumption time [MD＝－6.99， 95%CI （－8.27， －5.71）， P＜0.000 01]， and the incidence of postoperative reduced menstrual flow [RR＝0.25， 95%CI （0.12， 0.56）， P＝0.000 7] were significantly lower， less or shorter than control group； postoperative endometrial thickness [MD＝ 1.90， 95%CI （1.68， 2.13）， P＜0.000 01] and the rate of postoperative re-pregnancy [RR＝6.26， 95%CI （1.88， 20.83）， P＝0.003] were significantly higher than control group. CONCLUSIONS Dydrogesterone combined with estradiol valerate may reduce the incidence of IUA after induced abortion patients， decrease postoperative vaginal bleeding volume， shorten postoperative vaginal bleeding time and postoperative menstrual resumption time， and increase postoperative endometrial thickness.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.