[Analysis of clinical manifestations and prognosis of primary systemic light chain amyloidosis with liver involvement].

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results: The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 µmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2µmol/L group (0.178 years, 0.195 years) than with the TBil<34.2µmol/L group (0.750 years, 3.586 years) (P < 0.05). Conclusion: Mayo stage and hyperbilirubinemia are inferior prognostic factors for patients with primary systemic light chain amyloidosis accompanied with liver involvement.

Unveiling the temperature-dependent thermoelectric properties of the undoped and Na-doped monolayer SnSe allotropes: a comparative study.

Motivated by the excellent thermoelectric (TE) performance of bulk SnSe, extensive attention has been drawn to the TE properties of the monolayer SnSe. To uncover the fundamental mechanism of manipulating the TE performance of the SnSe monolayer, we perform a systematic study on the TE properties of five monolayer SnSe allotropes such asα-,ß-,γ-,δ-, andε-SnSe based on the density functional theory and the non-equilibrium Green's functions. By comparing the TE properties of the Na-doped SnSe allotropes with the undoped ones, the influences of the Na doping and the temperature on the TE properties are deeply investigated. It is shown that the figure of meritZTwill increase as the temperature increases, which is the same for almost all the Na-doped and undoped cases. The Na doping can enhance or suppress theZTin different SnSe allotropes at different temperatures, implying the presence of the anomalous suppression of theZT. The Na doping inducedZTsuppression may be caused basically by the sharp decrease of the power factor and the weak decrease of the electronic thermal conductance, rather than by the decrease of the phononic thermal conductance. We hope this work will be able to enrich the understanding of the manipulation of TE properties by means of dimensions, structurization, doping, and temperature.

Higher Cognitive Reserve Is Beneficial for Cognitive Performance Via Various Locus Coeruleus Functional Pathways in the Pre-Dementia Stage of Alzheimer's Disease.

BACKGROUND: Cognitive reserve (CR) shows protective effects on cognitive function in older adult and in Alzheimer's disease (AD). However, the brain mechanisms underlying the CR effect on the non-dementia AD spectrum (subjective cognitive decline (SCD) and mild cognitive impairment (MCI)) are unknown. The aim of this study was to investigate the potential moderate effect of CR on brain functional networks associated with cognitive performance. METHODS: We selected 200 participants, including 48 cognitively normal (CN) and 56 SCD, and 96 patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Seed-based locus coeruleus functional connectivity (LC FC) was conducted to detect early brain functional changes in the non-dementia AD spectrum. CR was assessed via years of education and intelligence (IQ). The ANDI composite executive function scores (ADNI-EF) and ADNI composite memory scores (ANDI-MEM) at baseline and 24-month follow-up were used to assess cognitive performance. RESULTS: Compared to the CN group, the SCD group showed abnormal LC FC with the executive control network (dorsolateral prefrontal cortex, DLPFC), salience network, sensorimotor network, reward network, and hippocampus, while these alterations were inverted at the MCI stage. The LC-hippocampus FC was correlated with ADNI-MEM at baseline and follow-up, and these relationships were moderated by education. The LC-DLPFC FC was correlated with ADNI-EF at baseline, and this association was moderated by IQ. CONCLUSION: Our results manifested that higher levels of CR would confer protective effects on SCD and MCI. Furthermore, IQ and education could moderate the relationship between LC FC and cognition through different pathways.

Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

[Efficacy and safety analysis of a combination regimen with BCL-2 inhibitor in relapsed/refractory primary systemic light chain amyloidosis with t(11;14) from a single center].

Objective: To explore the efficacy and safety of BCL-2 inhibitor-based treatment in patients with relapsed/refractory t (11; 14) primary systemic light chain amyloidosis. Methods: This was a retrospective case series study. Ten patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis who had all received treatment with a combination regimen including the BCL-2 inhibitor venetoclax from January 2018 to November 2022 at the Hematology Department of Peking University People's Hospital were included. Adverse events, and hematological and organ responses were evaluated. Results: The median age of the ten enrolled patients was 59 (range 41-78) years, and the male to female ratio was 8∶2. Except for one patient, a very good partial or better response was achieved in 8/9 patients and one patient obtained a partial response. The overall response rate was 100%. The median time to achieve a hematological response was 60 (range 24-236) days. At least one organ response was observed in 7/9 patients. With a median follow-up of 18 months, one patient experienced hematological progression and one patient died. Grade 3 adverse events included lymphocytopenia (3 cases), anemia (1 case), diarrhea (1 case), and appendicitis (1 case). One patient died of pulmonary fungal infection two months after completion of treatment, which was not excluded as being treatment related. Conclusion: A combination regimen including BCL-2 inhibitors in patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis is a potentially safe and effective treatment option that warrants further investigation.

[Radiation-associated sarcomas of bone and soft tissue: a clinicopathological analysis of 46 cases].

Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.

Electronic structures, transport properties, and optical absorption of bilayer blue phosphorene nanoribbons.

Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.

[Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor].

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION: The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

Spin-dependent thermoelectric transport properties of Cr-doped blue phosphorene.

We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.

[Analysis of the effects of low/intermediate dose of coagulation factor â § on 30 adult patients with severe hemophilia A in a single center].

Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.

[Mutation characteristics of osteosarcoma: a single center study of 64 cases using next-generation sequencing].

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.

[Pediatric myofibroma/myofibromatosis of the soft tissue and bone: a clinicopathological analysis of 28 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myofibroma/myofibromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.

Analysis of SOD1 variants in Chinese patients with familial amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, and genetic contributors exert a significant role in the complicated pathogenesis. Identification of the genetic causes in ALS families could be valuable for early diagnosis and management. The development of potential drugs for patients with genetic defects will shed new light on ALS therapy. AIM: To identify causative variants in three Chinese families with familial ALS (FALS), reveal the pathogenic mechanism and look for the targeted drug for ALS. DESIGN AND METHODS: Whole-exome sequencing and bioinformatics were used to perform genetic analysis of the ALS families. Functional analysis was performed to study the variants' function and search for potential drug targets. RESULTS: Three heterozygous missense variants of the superoxide dismutase 1 gene (SOD1) were identified in families with FALS. The clinical manifestations of these patients include spinal onset, predominant lower motor neurons presentation and absence of cognitive involvement. Functional analysis showed that all three SOD1 variants led to increased reactive oxygen species (ROS) levels, reduced cell viability and formation of cytoplasmic aggregates. Remarkably, the decreased cell viability induced by variants was rescued after treatment with the ROS inhibitor N-acetylcysteine. CONCLUSIONS: This study identified three SOD1 variants in three families with FALS. The variant SOD1 toxicity was associated with oxidative damage and aggregation, and N-acetylcysteine could rescue the decreased cell viability induced by these variants. Our findings support a pathogenic role for ROS in SOD1 deficiencies and provide a potential drug N-acetylcysteine for ALS therapy, especially in SOD1 patients with limb onset.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Retrospective analysis of short-term curative effect of total laparoscopic loop ileostomy reversal after radical resection of rectal cancer].

Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.