Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

In 2040, neurodegenerative diseases (NDD) will overtake cancer as the second leading cause of death after cardiovascular and cerebrovascular diseases. Therefore, the search for effective intervention measures has become the top priority to deal with this difficult burden. Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years to treat conditions such as decompression sickness, carbon monoxide poisoning and radiation damage. In recent years, studies have confirmed that HBOT has good effects in improving cognitive impairment after brain injury and stroke, and alleviating neurodegeneration and dysfunction related to NDD. Here we reviewed the pathogenesis and treatment state of NDD, introduced the application of HBOT in animal models and clinical studies of NDD, and expounded the application potential of HBOT in the treatment of NDD from the perspective of mitochondrial function, neuroinflammation, neurogenesis and angiogenesis, oxidative stress, apoptosis, microcirculation and epigenetics.
Hyperbaric Oxygenation ; Humans ; Neurodegenerative Diseases/physiopathology* ; Animals ; Oxidative Stress ; Apoptosis ; Mitochondria/physiology* ; Neurogenesis ; Epigenesis, Genetic

OBJECTIVE: To compare the clinical efficacy and complication rates of staged open reduction internal fixation (ORIF) and external fixation combined with limited internal fixation (EFLIF) in the treatment of high-energy Pilon fractures. METHODS: A retrospective selection was conducted on 78 patients diagnosed with high-energy tibial Pilon fractures who received treatment between January 2021 and October 2023. These patients were categorized into the staged ORIF group and the EFLIF group according to their respective treatment protocols. The staged ORIF group comprised 48 patients, including 29 males and 19 females, aged from 33 to 53 years old with a mean age of (43.25±4.67) years old. The time from injury to treatment averaged (6.54±2.21) hours. All patients received staged ORIF treatment. The EFLIF Group consisted of 30 patients, including 18 males and 12 females, aged from 36 to 54 years old with a mean age of (43.37±3.24) years old. The time from injury to treatment averaged (6.87±1.96) hours. All patients received EFLIF treatment. The recovery of ankle joint function, fracture reduction quality, fracture healing time, and surgical-related indicators between two groups were observed and compared six months after surgery. Additionally, the postoperative complications of the two groups were recorded. RESULTS: Both groups of patients were followed up and the duration ranged from 6 to 12 months, with an average of (8.97±1.26) months. At 6-month postoperative follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score in the ORIF group was (83.15±20.93), which did not show a statistically significant difference compared to the EFLIF group (81.88±20.67), P>0.05. The excellent and good rate of fracture reduction in the staged ORIF group was 33.33% (16/48), which did not show a statistically significant difference compared to the EFLIF group (30.00%, 9/30), P>0.05. The hospitalization duration and fracture healing time in the staged ORIF group were (16.57±1.25) days and (12.14±1.15) weeks, respectively. When compared to the EFLIF group, which demonstrated a hospitalization duration of (15.97±2.16 ) days and a fracture healing time of (12.36±1.17) weeks, no statistically significant differences were observed (P>0.05). The intraoperative blood loss in the staged ORIF group was (76.54±11.65) ml, which was significantly higher than that in the EFLIF group (70.15±10.29) ml, and the difference was statistically significant (P<0.05). The incidence of superficial tissue infection was 2.08%(1/48), which was significantly lower than that observed in the EFLIF group at 16.67% (5/30), and this difference was statistically significant (P<0.05). CONCLUSION Both staged ORIF and EFLIF were effective treatment options for high-energy closed Pilon fractures of the tibia. However, regarding the prevention of superficial tissue infection, staged ORIF demonstrates superior risk control compared to EFLIF.
Humans ; Male ; Female ; Middle Aged ; Adult ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; External Fixators ; Open Fracture Reduction/methods* ; Treatment Outcome

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic