OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

Breast cancer remains one of the frequently diagnosed malignant tumors among Chinese women,with hereditary cases accounting for 5%-10%of all diagnoses,where BRCA1/2 gene mutations serve as the primary genetic predisposition factors.Although targeted therapies like poly(ADP-ribose)polymerase(PARP)inhibitors have significantly improved prognoses for patients with BRCA-mutated breast cancer in recent years,critical clinical challenges persist,including the standardization of genetic testing protocols,optimization of precision treatment approaches,and refinement of long-term management strategies.In response to these challenges,our expert panel has conducted a comprehensive update to the 2018 Edition of this consensus by integrating the latest global evidence-based medical research with China's unique clinical practice characteristics.This 2025 Edition provides systematic evaluations and recommendations on five key aspects:indications for BRCA1/2 gene testing,testing methodologies,result interpretation,treatment strategies,and risk management.The main updates include:① Increasing the relationship between BRCA1/2 gene mutations and programmed death ligand-1(PD-L1)expression,as well as related content on BRCAness types;② Standardizing the application of genetic testing,such as increasing the significance,timing,and sample selection of clinical testing,and optimizing the BRCA testing population;③ Updating treatment strategies,such as non-drug treatment of BRCA1/2 gene mutation,treatment of triple negative breast cancer(TNBC)patients with BRCA1/2 gene mutation,treatment decisions of hormone receptor(HR)+/human epidermal growth factor receptor 2(HER2)-breast cancer patients with BRCA1/2 gene mutation,clinical use of PARP inhibitors and adverse reaction management;④ Addion of relevant content on long-term risk management,such as covering follow-up management,indications for preventive surgery,quality control and requirements for new genetic testing,updating genetic testing processes,report content and interpretation.This consensus aimed to establish standardized diagnostic and therapeutic frameworks for clinicians,advance precision medicine in BRCA-mutated breast cancer,and ultimately improve patient survival outcomes.As new evidence emerges,continuous updates will be implemented to incorporate the latest research findings.This consensus has been registered on the Practice guideline REgistration for transPAREncy(PREPARE)platform(registration number:PREPARE-2025CN1085).

Objective To explore the diagnostic and prognostic values of procalcitonin(PCT),interleukin 6(IL-6)and cystatin C(CysC)combined detection in sepsis acute kidney injury(AKI).Methods A total of 100 patients with sepsis were divided into the AKI group(n=56)and the non AKI group(n=44)according to the occurrence of AKI.The prognosis of AKI patients was followed up,and patients were divided into the survival group(n=32)and the death group(n=24)according to the presence or absence of death.Enzyme-linked immunosorbent assay(ELISA)was used to detect PCT,IL-6 and CysC in different groups of patients.The Acute Physiological Function and Chronic Health Status Score(APACHEⅡ)was used to assess the condition of illness.ROC curve was used to analyze the predictive values of PCT,IL-6 and CysC in the diagnosis and death of sepsis combined with AKI.Results The male ratio,age,hypertension with diabetes ratio,APACHE Ⅱ score,serum creatinine(Scr),PCT,IL-6 and CysC levels were higher in the AKI group than those in the non AKI group,and the ratio of complications and onset time were lower in the AKI group than those in the non AKI group(P＜0.05).The ROC curve results showed that the area under the curve(AUC)of PCT,IL-6,and CysC combined for the diagnosis of sepsis complicated with AKI was 0.859,with a sensitivity of 91.07%and a specificity of 90.91%.The combined diagnostic efficacy was better than that of a single indicator.The APACHE Ⅱ score,PCT,IL-6 and CysC levels were higher in the death group than those in the survival group(P＜0.05).The ROC curve results showed that the AUC,sensitivity and specificity of PCT,IL-6 and CysC combined in predicting mortality in sepsis patients with AKI were 0.847,91.67%and 87.50%,respectively.The combined predictive efficacy was better than that of single indicator.Conclusion The combination of PCT,CysC and IL-6 indicators is more valuable in diagnosing and predicting prognosis of sepsis with AKI.

Objective To investigate the influencing factor of prognosis of symptomatic intracranial large artery occlusive(ILAO)cerebral infarction in nonacute phase.Methods According to the prognosis,86 patients with symptomatic ILAO cerebral infarction in nonacute phase were divided into good prognosis group and poor prognosis group,and the clinical data of the two groups were compared.Multifactorial Logistic regression analysis was used to screen out the factors that influence prognosis.The related factors were combined to construct a nomogram for predicting poor prognosis of ILAO cerebral infarction in nonacute phase,validated by calibration curves and decision curve analysis.Results Compared with those in the good prognosis group,age,admission mRS,admission NIHSS score,globulin level and medication ratio in the poor prognosis group were significantly higher,and triacylglycerol level,albumin-globulin ratio in the poor prognosis group were significantly lower(P＜0.05-0.01).Multifactorial Logistic regression analysis showed that admission mRS was positively associated with poor 3-month prognosis of patients with ILAO cerebral infarction in nonacute phase(OR=2.551,95％CI:1.134-5.738,P=0.024);endovascular opening therapy was negatively associated with poor 3-month prognosis of patients with ILAO cerebral infarction in the nonacute phase(OR=0.132,95％CI:0.027-0.634,P=0.011).Incorporating admission mRS and endovascular opening treatment to establish a nomogram had good predictive efficacy.Conclusions Admission mRS and endovascular recanalization treatment increased and decreased the risk of poor prognosis at 3 months in patients with ILAO cerebral infarction in nonacute phase,respectively.The nomogram established by combining the two has good application value in predicting the poor prognosis of patients.

Breast cancer remains one of the frequently diagnosed malignant tumors among Chinese women,with hereditary cases accounting for 5%-10%of all diagnoses,where BRCA1/2 gene mutations serve as the primary genetic predisposition factors.Although targeted therapies like poly(ADP-ribose)polymerase(PARP)inhibitors have significantly improved prognoses for patients with BRCA-mutated breast cancer in recent years,critical clinical challenges persist,including the standardization of genetic testing protocols,optimization of precision treatment approaches,and refinement of long-term management strategies.In response to these challenges,our expert panel has conducted a comprehensive update to the 2018 Edition of this consensus by integrating the latest global evidence-based medical research with China's unique clinical practice characteristics.This 2025 Edition provides systematic evaluations and recommendations on five key aspects:indications for BRCA1/2 gene testing,testing methodologies,result interpretation,treatment strategies,and risk management.The main updates include:① Increasing the relationship between BRCA1/2 gene mutations and programmed death ligand-1(PD-L1)expression,as well as related content on BRCAness types;② Standardizing the application of genetic testing,such as increasing the significance,timing,and sample selection of clinical testing,and optimizing the BRCA testing population;③ Updating treatment strategies,such as non-drug treatment of BRCA1/2 gene mutation,treatment of triple negative breast cancer(TNBC)patients with BRCA1/2 gene mutation,treatment decisions of hormone receptor(HR)+/human epidermal growth factor receptor 2(HER2)-breast cancer patients with BRCA1/2 gene mutation,clinical use of PARP inhibitors and adverse reaction management;④ Addion of relevant content on long-term risk management,such as covering follow-up management,indications for preventive surgery,quality control and requirements for new genetic testing,updating genetic testing processes,report content and interpretation.This consensus aimed to establish standardized diagnostic and therapeutic frameworks for clinicians,advance precision medicine in BRCA-mutated breast cancer,and ultimately improve patient survival outcomes.As new evidence emerges,continuous updates will be implemented to incorporate the latest research findings.This consensus has been registered on the Practice guideline REgistration for transPAREncy(PREPARE)platform(registration number:PREPARE-2025CN1085).

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective To investigate the current symptom status of maintenance hemodialysis(MHD)patients,analyze the influencing factors from the perspective of multidimensional symptom burden,extract symptom groups,and construct a symptom network.Methods A total of 490 patients who received MHD at the blood purification center of a tertiary hospital in Shanghai from March to April 2025 were selected using a convenience sampling method.30 symptoms of MHD patients were investigated using a modified dialysis symptom index table.SPSS and R software were utilized to analyze the influencing factors,extract symptom groups,and construct a multidimensional symptom network.Results A total of 488 valid questionnaires were collected,with a valid questionnaire recovery rate of 99.59％.The median number of symptoms experienced by patients was 6(interquartile range:4,8),with the top 5 symptoms being dry skin(69.88％),fatigue or tiredness(56.97％),itching(56.97％),worry(50.20％),and dry mouth(46.31％).Multidimensional analysis indicated that age,duration of dialysis,education level,and complications were influencing factors of symptom burden scores across different dimensions.6 stable symptom groups were extracted,namely skin discomfort,fatigue and pain,gastrointestinal tract,sleep disorders,water-electrolyte imbalance,and uremia.The results of the symptom network analysis revealed that difficulty of falling asleep had the highest intensity centrality(rs=2.18,2.25,2.12).Conclusion The symptom association is relatively stable,and difficulty of falling asleep is the core symptom.This finding can assist clinical medical staff in achieving efficiency and precision in symptom group management.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.