1.Neuroprotective Mechanism of Yifei Xuanfei Jiangzhuo Prescription on VaD Rats Based on NF-κB/NLRP3 Signaling Pathway
Bingmao YUAN ; Wei CHEN ; Xiu LAN ; Lingfei JIANG ; Lin WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):88-96
ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway to improve neuronal function in vascular dementia (VaD) rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries (CCA) combined with bilateral vascular occlusion (2-VO). Eighty-four SD rats were randomly divided into a blank group, sham group, model group, piracetam group (0.2 g·kg-1), and low-, medium-, and high-dose Yifei Xuanfei Jiangzhuo prescription groups (6.09, 12.18, and 24.36 g·kg-1). Drug administration began on day 7 after surgery, once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin (HE) staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen (NeuN). Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase (IKK), NF-κB p65, NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), and interleukin-1β (IL-1β). ResultsCompared with the blank group, the model group showed a significant reduction in platform-crossing frequency (P0.01), aggravated hippocampal injury, a significant increase in neuronal apoptosis (P0.05), decreased NeuN positivity in the CA1 region (P0.05), increased nuclear expression of NF-κB p65 (P0.05), and significantly elevated expression of p-IKK, p-NF-κB p65, NLRP3, cleaved Caspase-1, ASC, and cleaved IL-1β (P0.05). Compared with the model group, all drug-treated groups improved learning and spatial memory in VaD rats, alleviated hippocampal pathological injury and neuronal apoptosis, and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg-1 reduced hippocampal expression levels of p-IKK, p-NF-κB p65, NLRP3, Caspase-1, ASC, and cleaved IL-1β in VaD rats (P0.05), showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway, thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.
2.Neuroprotective Mechanism of Yifei Xuanfei Jiangzhuo Prescription on VaD Rats Based on NF-κB/NLRP3 Signaling Pathway
Bingmao YUAN ; Wei CHEN ; Xiu LAN ; Lingfei JIANG ; Lin WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):88-96
ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway to improve neuronal function in vascular dementia (VaD) rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries (CCA) combined with bilateral vascular occlusion (2-VO). Eighty-four SD rats were randomly divided into a blank group, sham group, model group, piracetam group (0.2 g·kg-1), and low-, medium-, and high-dose Yifei Xuanfei Jiangzhuo prescription groups (6.09, 12.18, and 24.36 g·kg-1). Drug administration began on day 7 after surgery, once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin (HE) staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen (NeuN). Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase (IKK), NF-κB p65, NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), and interleukin-1β (IL-1β). ResultsCompared with the blank group, the model group showed a significant reduction in platform-crossing frequency (P0.01), aggravated hippocampal injury, a significant increase in neuronal apoptosis (P0.05), decreased NeuN positivity in the CA1 region (P0.05), increased nuclear expression of NF-κB p65 (P0.05), and significantly elevated expression of p-IKK, p-NF-κB p65, NLRP3, cleaved Caspase-1, ASC, and cleaved IL-1β (P0.05). Compared with the model group, all drug-treated groups improved learning and spatial memory in VaD rats, alleviated hippocampal pathological injury and neuronal apoptosis, and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg-1 reduced hippocampal expression levels of p-IKK, p-NF-κB p65, NLRP3, Caspase-1, ASC, and cleaved IL-1β in VaD rats (P0.05), showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway, thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.
3.Iodine nutrition status of pregnant women in Weihai City before and after iodine deficiency disorders intervention
Shuliang LIU ; Huaqiang SUN ; Guoying ZHANG ; Zhifang WANG ; Linqing XIU ; Lingfei ZHANG ; Yanjun WU ; Min YIN ; Lei LIN ; Shuai ZHAO
Chinese Journal of Endemiology 2025;44(4):313-317
Objective:To analyze the iodine nutrition status of pregnant women in Weihai City before and after (2022, 2023) the iodine deficiency disorders (IDD) intervention, evaluate the effectiveness of intervention measures, and provide a scientific basis for adjusting IDD prevention strategies in the city.Methods:In May 2023, the intervention action of IDD was carried out for pregnent women in Weihai City. In April 2022 and December 2023, respectively, a cross-sectional survey method was conducted in four districts (cities) of Weihai City. Each district (city) was divided into five areas (east, west, south, north, and central) each year, and one township (street) was selected from each areas. At least 20 pregnant women were selected from each township (street) as survey subjects, and their household salt samples and random urine samples were collected to measure salt iodine and urinary iodine concentrations, and to compare the test results.Results:A total of 922 household salt samples were tested, including 530 iodized salt samples and 469 qualified iodized salt samples. The median salt iodine was 24.00 mg/kg. The coverage rate of iodized salt, the qualified rate of iodized salt, and the consumption rate of qualified iodized salt were 57.48%, 88.49%, and 50.87%, respectively. No significant difference was observed in medians salt iodine between 2022 (24.26 mg/kg) and 2023 (24.00 mg/kg, Z = - 1.58, P = 0.113). However, the coverage rate of iodized salt and the consumption rate of qualified iodized salt in 2023 werehigher than those in 2022 [73.72% (373/506) vs 37.74% (157/416), 65.22% (330/506) vs 33.41% (139/416), χ 2 = 120.90, 92.40, P < 0.001]. A total of 922 urine samples were collected from pregnant women, with a median urinary iodine of 135.90 μg/L. The median urinary iodine of pregnant women in 2022 was 113.55 μg/L. There was a statistically significant difference in medians urinary iodine among different regions ( H = 27.91, P < 0.001). The median urinary iodine of pregnant women in 2023 was 153.00 μg/L. There was no statistically significant difference in medians urinary iodine among different regions ( H = 3.33, P = 0.343). The medians urinary iodine of pregnant women in Huancui District, Wendeng District, and Rushan City in 2023 (156.60, 155.00, 140.85 μg/L) were higher than those in 2022 (93.60, 110.00, 110.70 μg/L), and the differences were statistically significant ( Z = - 5.44, - 4.92, - 5.99, P < 0.001). The median urinary iodine of pregnant women in Weihai City in 2023 showed a statistically significant difference compared to 2022 ( Z = - 7.62, P < 0.001). Conclusions:The IDD intervention measures in Weihai City have achieved good results, and the coverage of iodized salt, the consumption rate of qualified iodized salt, and the iodine nutrition level of pregnant women have improved. We should continue to implement intervention measures, improve the iodine nutrition level of key populations, and maintain a sustained elimination of IDD.
4.Human leukocyte antigen matched sibling fresh cord blood transplantation for beta-thalassaemia major in children
Jianyun WEN ; Libai CHEN ; Yuelin HE ; Xiaoqin FENG ; Xuan LIU ; Xiaoxiao XU ; Xiu LI ; Qiujun LIU ; Xuedong WU
Chinese Journal of Tissue Engineering Research 2025;29(23):4899-4906
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98%and 89%,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1%.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.
5.Dihydromyricetin attenuates Ang Ⅱ-induced cardiac hypertrophy in mice through activation of AMPK/PPAR-α signaling pathway
Xiao-ying ZHANG ; Jia-jia WU ; Qi SI ; Guo-xiu WU ; Liang ZHANG ; Zhi-ying ZHANG
Chinese Pharmacological Bulletin 2025;41(10):1914-1921
Aim To investigate the effect of dihydro-myricetin(DMY)on Ang Ⅱ-induced cardiac hypertro-phy in mice and the underlying mechanisms.Methods Fifty mice were randomly divided into control group,Ang Ⅱ group,Ang Ⅱ+catopril 12.0 mg·kg-1·d-1 group,AngⅡ+DMY 100 mg·kg-1·d-1 group,and Ang Ⅱ+DMY 200 mg·kg-1·d-1 group,with 10 mice in each group.The control mice were given saline by gavage,the drug intervention group was given DMY,and the positive drug group was given captopril;the mice in all groups except the control group were in-jected subcutaneously with Ang Ⅱ 1.0mg·kg-1·d-1.After four weeks,heart weight/body weight(HW/BW)and left ventricular weight/body weight(LVW/BW)ratios were calculated.The mRNA ex-pression of the fetal genes atrial natriuretic factor(ANF),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),adenosine triphosphate 5β-subunit(ATP 5β)and uncoupling protein 2(UCP2)were monitored,and the morphological changes of car-diac tissue were observed.Secondly,the creatine ki-nase isoenzyme(CK-MB),lactate dehydrogenase(LDH),free fatty acids(FFA)and lactic acid in ser-um were investigated.Lastly,the expression of AMP-activated proteinkinase(AMPK),peroxisome prolifer-ator-activated receptor alpha(PPAR-α)and T-cell nu-clear factor cytoplasmic 4(NFATc4)protein expres-sion were also detected.The Ang Ⅱ-induced H9C2 cardiomyocyte hypertrophy model was established and treated with the AMPK inhibitor compound C.The mRNA of ANF,BNP,β-MHC and the protein expres-sion of AMPK/PPAR-α were analyzed.Results DMY intervention significantly reduced HW/BW and LVW/BW in mice,fetal genes ANF,BNP,β-MHC and UCP2 mRNA expression decreased,whereas ATP 5 β mRNA increased,and the degree of hypertrophy of cardiomyocytes was alleviated.In addition,the serum levels of CK-MB,LDH,FFA and lactic acid were re-duced in DMY treated groups.Finally,DMY upregu-lated the protein expression of P-AMPK,AMPK and PPAR-α,and downregulated protein expression of NFATc4.In the Ang Ⅱ-induced cardiomyocyte hyper-trophy model,DMY pretreatment reduced the mRNA expression of fetal genes(ANF,BNP,β-MHC).However,when AMPK was inhibited by compound C,the expression of these fetal genes rebounded,accom-panied by decreased protein levels of AMPK and PPAR-α.Conclusions DMY can improve Ang Ⅱ-in-duced myocardial hypertrophy in mice by ameliorating disorders of glycolipid metabolism and increasing ener-gy supply to cardiomyocytes,and its mechanism is re-lated to the activation of the AMPK/PPAR-α pathway and the inhibition of NFATc4 expression.
6.Study on mechanism of Jiawei Shaofu Zhuyu decoction in treatment of endometriosis fibrosis based on mitophagy
Can-can HUANG ; Wen-wen WAN ; Xiu-jia JI ; Bin YUE ; Yu-gui ZHANG ; Xiao-hua ZHANG ; Li LIANG ; Guo-lian CHEN ; Quan-sheng WU ; Hai-yan MAO
Chinese Pharmacological Bulletin 2025;41(6):1177-1185
Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.
7.Study on mechanism of Jiawei Shaofu Zhuyu decoction in treatment of endometriosis fibrosis based on mitophagy
Can-can HUANG ; Wen-wen WAN ; Xiu-jia JI ; Bin YUE ; Yu-gui ZHANG ; Xiao-hua ZHANG ; Li LIANG ; Guo-lian CHEN ; Quan-sheng WU ; Hai-yan MAO
Chinese Pharmacological Bulletin 2025;41(6):1177-1185
Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.
8.Human leukocyte antigen matched sibling fresh cord blood transplantation for beta-thalassaemia major in children
Jianyun WEN ; Libai CHEN ; Yuelin HE ; Xiaoqin FENG ; Xuan LIU ; Xiaoxiao XU ; Xiu LI ; Qiujun LIU ; Xuedong WU
Chinese Journal of Tissue Engineering Research 2025;29(23):4899-4906
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98%and 89%,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1%.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.
9.Atypical fibroxanthoma:clinicopathological features and prognostic analysis of 15 cases
Jiaying LIU ; Cui LIU ; Junhua WU ; Huizhen LI ; Xiu NIE ; Guixiang XIAO
Chinese Journal of Clinical and Experimental Pathology 2025;41(8):1044-1049
Purpose To investigate the clinicopathological features,differential diagnosis and prognosis of atypical fibroxanthoma(AFX).Methods Pathological features of 15 cases of AFX and 3 cases of pleomorphic dermal sarcoma(PDS)misdiagnosed as AFX were retrospectively analyzed by hematoxylin and eosin staining and immunohistochemical EnVision staining technology.Clinical information was collected and analyzed,and the relevant literatures were re-viewed.Results The age of the 15 patients with AFX ranged from 18 to 78 years,with an average age of 57 years.4 cases occurred in the head and neck,and 11 cases occurred in the trunk and limbs.3 patients with PDS misdiagnosed as AFX were aged from 56 to 60 years,with an average age of 58 years.The tumors were located in the trunk and limbs.Microscopically,15 cases of AFX and 3 cases of PDS misdiagnosed as AFX were composed of proliferative pleo-morphic and atypical spindle cells interspersed with a varying number of multinucleated cells.15 cases of AFX tumors were superficial and located in the dermis.In 3 cases of PDS misdiagnosed as AFX,1 case was located in subcutane-ous adipose tissue,1 case had superficial subcutaneous extension,and the third case had positive basal margin.Immu-nohistochemically,the immunophenotypes of the two groups were consistent.CD10 was expressed in all cases,CD68 was positive in most cases,SMA was expressed in a few cases,desmin was focal expressed in a very few cases,and S-100,SOX10,CD34,HMB-45,Melan A,STAT6 and CK(AE1/AE3)were not expressed in all cases.Ki67 prolifera-tion index ranged from 2%to 30%.15 patients with AFX were followed up from 12 to 108 months.One patient had tumor recurrence 1 year and 3 years after operation due to positive basal margin.Most of the other patients underwent extended resection after diagnosis and were in good condition without tumor recurrence and metastasis.3 cases of PDS misdiagnosed as AFX were followed up for 31 to 78 months.One patient had lung metastasis after 2 years,one patient recurred 4 times after operation,and the other patient died after 4 times of recurrence.Conclusion AFX is a rare dis-ease with similar pathological characteristics and immunophenotype to PDS.AFX can be diagnosed only when the tumor is small and completely confined to the dermis.When the maximum diameter of the tumor is more than 3 cm,or the presence of any form of subcutaneous extension requires a high level of vigilance for PDS.Careful differentiation and correct classification of AFX and PDS are very important for the treatment and prognosis of the disease.
10.Construction of a three-level early warning model for moderate to severe ovarian hyperstimulation syndrome in assisted reproductive technology
Zhufeng WU ; Jun LIU ; Chunlin LIU ; Qinhong LUO ; Fengxiang LI ; Xiu ZHANG
Chinese Journal of Reproduction and Contraception 2025;45(2):162-171
Objective:To construct and validate a three-level early warning model of moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology.Methods:A case-control study was conducted. Totally 10 181 infertility patients who underwent in vitro fertilization treatment in Reproductive Medicine Center, Women and Children's Medical Center Affiliated to Guangzhou Medical University from April 2013 to April 2023 were retrospectively analyzed and divided into modeling group (8 145 cases) and validation group (2 036 cases) by random number table method. The clinical data of the two groups were analyzed, and the risk factors affecting the occurrence of moderate and severe OHSS after oocytes retrieval were screened by multi-factor logistic regression analysis. The early warning model was established and the column diagram was drawn at three nodes which were before ovarian stimulation, before trigger and 3 d after oocyte retrieval. The receiver operating characteristic (ROC) curve and calibration curve were used to verify the models. Results:The antral follicle count (AFC, OR=1.045, 95% CI: 1.020-1.071, P<0.001), anti-Müllerian hormone (AMH)>3.36 μg/L ( OR=7.135, 95% CI: 2.084-24.432, P=0.002) and number of cycles ( OR=0.149, 95% CI: 0.022-1.026, P=0.049) were included in the pre-stimulation prediction model. AFC ( OR=1.046, 95% CI: 1.018-1.074, P=0.001), AMH>3.36 μg/L ( OR=5.780, 95% CI: 1.661-20.116, P=0.006), gonadotropin releasing hormone-agonist protocols ( OR=3.895, 95% CI=1.913-7.931, P<0.001), estrogen peak≥18 350 pmol/L ( OR=2.258, 95% CI: 1.092-4.666, P=0.028), the number of follicles with a diameter of ≥10 mm>20 ( OR=2.377, 95% CI: 1.092-5.172, P=0.029) were included in the pre-trigger prediction model. AMH>3.36 μg/L ( OR=8.374, 95% CI: 2.417-29.019, P=0.001), estrogen peak≥18 350 pmol/L ( OR=3.947, 95% CI: 1.533-10.167, P=0.004), total number of oocytes retrived ( OR=1.042, 95% CI: 0.996-1.090, P=0.025), abdominal distension ( OR=60.181, 95% CI: 22.515-160.854, P<0.001), fresh transplantation ( OR=21.766, 95% CI: 7.119-66.544, P<0.001), human chorionic gonadotropin trigger ( OR=17.752, 95% CI: 3.993-78.924, P<0.001) were included in the prediction model of 3 d after oocyte retrieval. The areas under ROC curves of the three models were 0.830 (95% CI: 0.782-0.878), 0.859 (95% CI: 0.812-0.906) and 0.948 (95% CI: 0.919-0.977), respectively. The areas under ROC curves of the validation groups of the three models were 0.922 (95% CI: 0.880-0.965), 0.936 (95% CI: 0.886-0.986), and 0.971 (95% CI: 0.938-0.999), respectively. The calibration curve indicated that the early-warning evaluation model has good stability. Conclusion:The three-level early warning model of moderate and severe OHSS has good differentiation, reliable predictability and clinical practicability, which is conducive to the dynamic and continuous assessment of the risk of moderate and severe OHSS, adjustment of treatment plan at any time, and timely adoption of effective preventive measures.

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