Pan vascular disease （PVD） is a systemic vascular disorder that has become the leading cause of death among the Chinese residents， and there is currently a lack of effective systemic treatment options. Clinical practice has found that the traditional Chinese medicine （TCM） method of kidney tonification can effectively intervene in PVD and target key pathological mechanisms of PVD recognized in Western medicine. Accordingly， this paper conducts research from the following three aspects： First， it clarifies that immune dysregulation， metabolic disorders， and genetic susceptibility constitute the core pathological mechanisms of PVD in Western medicine. Typical pathological manifestations include progressive vascular endothelial injury， lipid deposition， and plaque formation， ultimately leading to multi-organ damage and dysfunction. PVD activates pathways such as the NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， triggering immune dysregulation； it also induces disorders of mitochondrial energy metabolism， water-salt metabolism， and hormonal metabolism， synergizing with genetic susceptibility factors （e.g.， apolipoprotein E gene） to accelerate vascular homeostasis imbalance. Second， this study analyzes the intrinsic relationship between the TCM theory of "kidney deficiency" and the "immune-metabolic-genetic" axis， revealing the theoretical basis for kidney tonification in intervening PVD. The kidney stores essence， governs bones， and produces marrow， which is related to the generation and differentiation of immune cells. It regulates Qi transformation and governs water， overseeing material and energy metabolism. The kidney is the root of congenital essence and governs reproduction， closely related to genetic mechanisms. Third， by integrating modern clinical research， this study elaborates on the unique advantages and clinical value of kidney tonification in targeting the "immune-metabolic-genetic" axis of heart， brain， and kidney organs. Traditional kidney-tonifying formulas and their active ingredients improve immune-inflammatory responses， enhance material and energy metabolism homeostasis， and modulate epigenetic pathways through multiple pathways， targeting various pathways to intervene in PVD. This study systematically elucidates the scientific connotation of kidney tonification in treating PVD， providing theoretical support and practical guidance for integrated TCM-Western medicine approaches and contributing to innovation and improvement in diagnostic and treatment strategies for PVD.

Geniposide， the primary active component of the traditional Chinese medicine Gardeniae Fructus， is a water-soluble iridoid glycoside. Pharmacological studies have demonstrated that geniposide exhibits various biological activities， including hepatoprotective， anti-inflammatory， analgesic， neuroprotective， antidepressant effects， and inhibitory activity against ischemia-reperfusion injury. Recent research has revealed its promising potential in preventing and treating diseases such as atherosclerosis and osteoporosis， indicating broad application prospects. Numerous in vitro and in vivo studies indicate that the pharmacodynamic mechanisms of geniposide are primarily associated with the inhibition of inflammatory responses and oxidative stress， improvement of lipid metabolism， and regulation of apoptosis. However， due to its high water solubility and rapid metabolism in vivo， geniposide suffers from low oral bioavailability， which limits its therapeutic efficacy and clinical application. In recent years， various formulations， such as creams， cubic liquid crystals， hydrogels， and liposomes， have been developed to address its bioavailability issues. This article reviewed the latest research progress on the pharmacological activities and formulation development of geniposide by analyzing domestic and international literature from the past decade， aiming to provide a theoretical basis for further research， development， and utilization of geniposide and its formulations.

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

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

AIM:To analyze the expression of se-creted phosphoprotein 1(SPP1)and programmed cell death-ligand 1(PD-L1)in SMARCA4-deficient non-small cell lung cancer,and to provide a scientif-ic basis for the study of the follow-up treatment of this rare pathological type of lung cancer.METH-ODS:The clinical and pathological characteristics of 12 patients with this disease were analyzed retro-spectively,and the patients were divided into two groups of adenocarcinomas and poorly differentiat-ed carcinomas according to their morphological characteristics,and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups.RESULTS:SPP1 expression was detect-ed in all patients and Its expression level was signif-icantly higher in the poorly differentiated carcino-ma group compared with the adenocarcinoma group(P=0.015);PD-L1 expression was found in 6/7 patients(5 cases were not measured),compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carci-noma group(P=0.048)and the PD-L1 difference be-tween the two groups suggested that the results were similar to those of SPP1.CONCLUSION:SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1.It was more pronounced in patients with poorly differenti-ated carcinoma.There may be a positive correla-tion between SPP1 and PD-L1 expression in SMAR-CA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies.

Extracorporeal membrane oxygenation (ECMO) serves as an advanced life support technology and plays a critical role in treating critically ill patients with severe cardiopulmonary failure. However, the unique physiological and pathological changes during pregnancy present numerous challenges and special considerations for the application of ECMO in obstetrics. Given the current lack of unified guidelines specifically for obstetric ECMO, clinical practice often relies on adapting general ECMO guidelines in combination with obstetric-specific factors. This article systematically reviews the core principles of existing general ECMO guidelines, provides an in-depth analysis of the impact of gestational physiological and pathological characteristics on ECMO application, and discusses the particularities and necessary adaptations of obstetric ECMO in terms of indications, anticoagulation strategies, parameter adjustment, multidisciplinary collaboration, and emergency management. Furthermore, it proposes strategies suitable for domestic clinical practice. The article also addresses existing difficulties and limitations not covered by current guidelines and calls for the urgent development of specialized obstetric ECMO guidelines to provide clinicians with more standardized and safer decision-making support, ultimately improving outcomes for critically ill pregnant patients and newborns.

Objective:To investigate the structural changes in the spinal cord in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and their relationship with clinical disability.Methods:This study was cross-sectional. A retrospective analysis of clinical and imaging data from 124 patients with MS (MS group), 101 patients with aquaporin-4 antibody-positive NMOSD (NMOSD group), and 110 healthy controls (HC group) from seven medical centers were conducted from January 2018 to October 2021. All subjects underwent 3D T 1WI, and the upper cervical spinal cord cross-sectional area (MUCCA) was segmented and measured. All patients completed the expanded disability status scale (EDSS) assessments at baseline and during follow-up, as well as the baseline 25-foot walk test (T25FW) and the nine-hole peg test (NHPT). Patients were classified into EDSS progression and non-progression groups based on follow-up EDSS scores. Comparisons of MUCCA among the three groups were conducted using analysis of covariance, controlling for age and sex as covariates. Pairwise comparisons between groups were performed using the HSD test. Univariate linear regression and logistic models were employed to identify candidate predictors of baseline clinical disability status or EDSS progression in the MS and NMOSD groups. L1 regularized multivariable linear regression analysis was used to determine independent predictors of baseline clinical disability status or EDSS progression. Independent predictors were then combined to establish a logistic regression model, and the model′s performance in predicting EDSS progression was evaluated using receiver operating characteristic analysis and the area under the curve (AUC). Results:A total of 144 patients completed follow-up EDSS assessments, with a follow-up duration of 3.30 (1.10, 6.42) years, including 82 patients in the MS group and 62 patients in the NMOSD group. Controlling for sex and age as covariates, the overall difference in MUCCA among the MS, NMOSD, and HC groups was statistically significant ( P=0.001). The MUCCA in the MS group was lower than that in the HC group, with a significant difference ( t=-2.54, P=0.007); the MUCCA in the NMOSD group was also lower than that in the HC group, with a significant difference ( t=-2.80, P=0.002). However, the difference in MUCCA between the MS and NMOSD groups was not statistically significant ( t=-0.40, P=0.882). In the MS group, MUCCA was an independent predictor of baseline EDSS score (β=-0.03), baseline T25FW score (β=-0.09), and baseline NHPT score (β=-0.30). In the NMOSD group, MUCCA (β=-0.08), age (β=0.06), and baseline EDSS score (β=-0.43) were independent predictors of EDSS progression, and the logistic regression model incorporating these three factors predicted EDSS progression with an AUC of 0.82. Conclusions:Significant spinal cord atrophy occurs in patients with both MS and NMOSD. Atrophy of the upper cervical spinal cord can predict the degree of disability in MS patients and the progression of clinical disability in NMOSD patients.

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective To utilize single-cell and peripheral blood transcriptomic data from 3D brain organoids,combined with machine learning,to analyze the role of mitochondrial autophagy genes in schizophrenia(SCZ).Methods By integrating two machine learning algorithms,we identified differentially expressed mitochondrial autophagy-related genes between schizophrenia patients and healthy controls using peripheral blood RNA sequencing data.The relationship between mitophagy gene,immune cells and inflammatory factors was further explored.Comprehensive single-cell analysis was used to explore the signaling pathways and specific transcription factors based on mitophagy genes.Results Using machine learning,seven key mitophagy genes expressed in schizophrenia patients were identified.Based on Mitoscore analysis,at the single-cell level,neurons with high mitochondrial autophagy activity(Mitohigh_Neuron)formed new interactions with endothelial cells via the SPP1 signaling pathway.Conclusion This study identified two subtypes of mitophagy and seven key mitophagy genes in schizophrenia,providing new insights into the pathogenesis of the disease.