A Neglected Gene: The Role of the ANG Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a poor prognosis. To date, more than 40 ALS-related genes have been identified. However, there is still a lack of targeted therapeutic drugs for the treatment of ALS, especially for patients with acute onset and severe disease. A series of studies reported missense heterozygous mutations with loss of function in the coding region of the ANG gene in ALS patients. ANG deficiency is related to the pathogenesis of ALS, but the underlying mechanism has not been determined. This article aimed to synthesize and consolidate the knowledge of the pathological mechanism of ALS induced by ANG mutation and provide a theoretical basis for ALS diagnosis and targeted therapy. This article further delves into the mechanisms underlying the current understanding of the structure and function of the ANG gene, the association between ANG and ALS, and its pathogenesis. Mutations in ANG may lead to the development of ALS through the loss of neuroprotective function, induction of oxidative stress, or inhibition of rRNA synthesis. ANG mutations and genetic and environmental factors may cause disease heterogeneity and more severe disease than in ALS patients with the wild-type gene. Exploring this mechanism is expected to provide a new approach for ALS treatment through increasing ANG expression or angiogenin activity. However, the related study is still in its infancy; therefore, this article also highlights the need for further exploration of the application of ANG gene mutations in clinical trials and animal experiments is needed to achieve improved early diagnosis and treatment of ALS.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.

Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.

Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

SOX4 as a potential therapeutic target for pathological cardiac hypertrophy.

Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.

Effects of Transcranial Direct Current Stimulation on Endurance Performance of Lower Limbs:A Systematic Review / 医用生物力学

Sports fatigue of the lower limbs is one of the important factors affecting sports performance. How to improve the anti-fatigue ability of the lower limbs during endurance exercise is the focus of the research field of human sports biomechanics. This study systematically reviewed the relevant literature on transcranial direct current stimulation (tDCS) intervention on lower limb endurance performance, summarized the effect of tDCS on lower limb endurance performance, and analyzed the influencing factors and potential mechanisms. The results showed that: tDCS intervention has a significant effect on the endurance performance of the whole lower limbs, but there is no unified conclusion on the effect on the endurance performance of the knee joint. The researchers deem that tDCS can increase the excitability of the primary motor cortex and reduce the activation of the supplementary motor area and the premotor area to producing a lower rating of perceived exertion, but cannot affect the perception of exercise-induced pain, and stimulation protocols varied across studies, which may be partly responsible. This study can provide a theoretical basis for exploring the central mechanism of tDCS to improve endurance performance, formulating rehabilitation and sports training programsfor different groups of people, and developing new stimulation equipment to enhance the human body’s anti fatigue ability.

Comparison of clinical outcomes among total knee arthroplasties using posterior-stabilized, cruciate-retaining, bi-cruciate substituting, bi-cruciate retaining designs: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Despite the advent of innovative knee prosthesis design, a consistent first-option knee implant design in total knee arthroplasty (TKA) remained unsettled. This study aimed to compare the clinical effects among posterior-stabilized (PS), cruciate-retaining (CR), bi-cruciate substituting (BCS), and bi-cruciate retaining designs for primary TKA.@*METHODS@#Electronic databases were systematically searched to identify eligible randomized controlled trials (RCTs) and cohort studies from inception up to July 30, 2021. The primary outcomes were the range of knee motion (ROM), and the secondary outcomes were the patient-reported outcome measures (PROMs) and complication and revision rates. Confidence in evidence was assessed using Confidence in Network Meta-Analysis. The Bayesian network meta-analysis was performed for synthesis.@*RESULTS@#A total of 15 RCTs and 18 cohort studies involving 3520 knees were included. The heterogeneity and inconsistency were acceptable. There was a significant difference in ROM at the early follow-up when PS was compared with CR (mean difference [MD] = 3.17, 95% confidence interval [CI] 0.07, 7.18) and BCS was compared with CR (MD = 9.69, 95% CI 2.18, 17.51). But at the long-term follow-up, there was no significant difference in ROM in any one knee implant compared with the others. No significant increase was found in the PROMs and complication and revision rates at the final follow-up time.@*CONCLUSIONS@#At early follow-up after TKA, PS and BCS knee implants significantly outperform the CR knee implant in ROM. But in the long run, the available evidence suggests different knee prostheses could make no difference in clinical outcomes after TKA with extended follow-up.

METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

Research progress of optic atrophy 1-mediated mitochondrial dynamics in skeletal system diseases / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of mitochondrial dynamics mediated by optic atrophy 1 (OPA1) in skeletal system diseases.@*METHODS@#The literatures about OPA1-mediated mitochondrial dynamics in recent years were reviewed, and the bioactive ingredients and drugs for the treatment of skeletal system diseases were summarized, which provided a new idea for the treatment of osteoarthritis.@*RESULTS@#OPA1 is a key factor involved in mitochondrial dynamics and energetics and in maintaining the stability of the mitochondrial genome. Accumulating evidence indicates that OPA1-mediated mitochondrial dynamics plays an important role in the regulation of skeletal system diseases such as osteoarthritis, osteoporosis, and osteosarcoma.@*CONCLUSION@#OPA1-mediated mitochondrial dynamics provides an important theoretical basis for the prevention and treatment of skeletal system diseases.

Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.@*METHODS@#The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.@*RESULTS@#Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.@*CONCLUSION@#The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.

Comparison of filling ratio, alignment, and stability between ABG Ⅱ short-stem and Corail long-stem in total hip arthroplasty for Dorr type C femur / 中国修复重建外科杂志

OBJECTIVE@#Using the mono-energy reconstruction images and X-ray films to investigate whether the ABG Ⅱ short-stem could improve the filling ratio, stability, and alignment in the Dorr type C femur, compared with the Corail long-stem.@*METHODS@#Among patients who were with Dorr type C femurs and treated with total hip arthroplasty between January 2006 and March 2012, 20 patients with a Corail long-stem (Corail group) and 20 patients with an ABG Ⅱ short-stem (ABG Ⅱ group) were randomly selected. The differences in gender, age, body mass index, and preoperative diagnoses between the two groups were not significant ( P>0.05). The ABG Ⅱ group was with a mean follow-up of 142 months (range, 102-156 months), and the Corail group was with a mean follow-up of 107 months (range, 91-127 months). There was no significant difference in the Harris score and subjective satisfaction score between the two groups at last follow-up ( P>0.05). At last follow-up, dual-energy CT scans with mono-energy image reconstruction were used to calculate the prosthetic filling ratio and to measure the alignment of the prosthesis in the coronal and sagittal positions. Stability assessment was performed based on X-ray films, and the subsidence distance was measured using EBRA-FCA software.@*RESULTS@#X-ray film observation showed that the prostheses in the two groups were stable and no signs of loosening was found. The incidence of pedestal sign was significantly lower in the ABGⅡ group than in the Corail group ( P<0.05), and the incidence of heterotopic ossification was significantly higher in the ABGⅡ group than in the Corail group ( P<0.05). The subsidence distance of femoral stem in ABG Ⅱ group was significantly greater than that in Corail group ( P<0.05), and the subsidence speed of femoral stem in ABG Ⅱ group was also greater than that in Corail group, but the difference was not significant ( P>0.05). The overall prosthesis filling ratio was significantly higher in the ABG Ⅱ group than in the Corail group ( P<0.05), while the coronal filling ratio at the lesser trochanter, 2 cm below the lesser trochanter, and 7 cm below the lesser trochanter were not significant ( P>0.05). The results of prosthesis alignment showed that there was no significant difference in the sagittal alignment error value and the incidence of coronal and sagittal alignment error >3° between the two groups ( P>0.05), while the coronal alignment error value in the ABG Ⅱ group was significantly greater than that in the Corail group ( P<0.05).@*CONCLUSION@#Although the ABG Ⅱ short-stem avoids the distal-proximal mismatch of the Corail long-stem in the Dorr type C femur and thus achieves a higher filling ratio, it does not appear to achieve better alignment or stability.

Influence of patellofemoral joint degeneration on clinical outcomes after medial unicompartmental knee arthroplasty / 中华医学杂志(英文版)

BACKGROUND@#Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA.@*METHODS@#Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic.@*RESULTS@#A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = -2.18, P   <  0.01) and KSS (MD = -2.61, P   <  0.01). The severity degree of PFJ degeneration had no additional adverse effect on the OKS, KSS, or revision rates. For mobile-bearing UKA, only lateral PFJ degeneration significantly decreased the OKS (MD = -2.21, P  < 0.01) and KSS (MD = -2.44, P  < 0.01). For fixed-bearing UKA, no correlation was found between PROMs/revision rates and PFJ degeneration.@*CONCLUSION@#For medial mobile-bearing UKA, slight to moderate degenerative changes in the PFJ, except lateral facet, did not compromise PROMs or revision rates. For medial fixed-bearing UKA, although it might not be conclusive enough, PROMs or revision rates were not adversely affected by PFJ degeneration (regardless of the facet).

Simulation Study of FEUDT Structure Optimization and Sensitive Film Loading of SAW Devices.

In order to further improve the degree of frequency response of the surface acoustic wave (SAW) sensor for gas detection, the structure of the forked-finger transducer was analyzed, and its optimal structural parameters were simulated and designed. The simulation model of the unidirectional fork-finger transducer is established by using COMSOL finite element software. The thickness of the piezoelectric substrate, the electrode structure and material, and the thickness of the coating film are optimized and simulated. The results show that: the optimal thickness of the piezoelectric substrate is 3λ. The optimal thickness ratio and the lay-up ratio of the forked-finger electrode are 0.02 and 0.5, respectively. The Al electrode is more suitable as the a forked-finger electrode material compared to Cu, Au and Pt materials. Under the same conditions, the metal oxide-sensitive film (ZnO and TiO2) has a higher frequency response than the polymer-sensitive film (polyisobutylene and polystyrene), and the best sensitive film thickness range is 0.5~1 µm.

WITHDRAWN: A deep learning framework for diagnosing periprosthetic joint infections using X-ray images: a discovery and validation study.

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SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology

The neurotropism of SARS-CoV-2 and the phenotypes of infected neurons are still in debate. Long COVID manifests with "brain diseases" and the cause of these brain dysfunction is mysterious. Here, we analyze 34 age- and underlying disease-matched COVID-19 or non-COVID-19 human brains. SARS-CoV-2 RNA, nucleocapsid, and spike proteins are present in neurons of the cognitive centers of all COVID-19 patients, with its non-structural protein NSF2 detected in adult cases but not in the infant case, indicating viral replications in mature neurons. In adult COVID-19 patients without underlying neurodegeneration, SARS-CoV-2 infection triggers A{beta} and p-tau deposition, degenerating neurons, microglia activation, and increased cytokine, in some cases with A{beta} plaques and p-tau pretangles. The number of SARS-CoV-2+ cells is higher in patients with neurodegenerative diseases than in those without such conditions. SARS-CoV-2 further activates microglia and induces A{beta} and p-tau deposits in non-Alzheimers neurodegenerative disease patients. SARS-CoV-2 infects mature neurons derived from inducible pluripotent stem cells from healthy and Alzheimers disease (AD) individuals through its receptor ACE2 and facilitator neuropilin-1. SARS-CoV-2 triggers AD-like gene programs in healthy neurons and exacerbates AD neuropathology. An AD infectious etiology gene signature is identified through SARS-CoV-2 infection and silencing the top three downregulated genes in human primary neurons recapitulates the neurodegenerative phenotypes of SARS-CoV-2. Thus, our data suggest that SARS-CoV-2 invades the brain and activates an AD-like program.

Research and comparison of electronic data capture systems used in clinical researches / 中华医学科研管理杂志

Objective:To provide a reference for the choice of electronic data capture system used in clinical research, the function and performance of some tool software were expounded and compared.Methods:We selected three freely available systems of REDCap, Commcare, and OpenEDC as research objects, describing and comparing their user license acquisition path, data capture related functions, and information security assurance measures. This article reflected how the three kinds of tool software ensure research data privacy and scientificity, and presented the consideration of system security and accessibility.Results:REDCap was the most mature system of the three, which had a fairly comprehensive design in functional integrity, data security, user friendliness, and system scalability. Commcare system featured in the mobile collection, and supported the most abundant types of collected data, while OpenEDC was characteristic of low threshold and flexible deployment.Conclusions:REDCap system is widely applicable to small and medium scale medical research, including clinical trials, retrospective studies, cohort studies, and translational research. Commcare system is the preferred option for medical investigations represented by epidemiologic surveys, while OpenEDC is particularly suitable for investigator initiated studies.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Risk analysis of brain metastases in limited-stage small cell lung cancer (LS-SCLC)achieving complete remission after thoracic radio-chemotherapy / 中华放射肿瘤学杂志

Objective:Small cell lung cancer (SCLC) is a highly malignant tumor with a high risk of brain metastasis (BMs). The purpose of this study was to evaluate the clinical factors affecting the occurrence of BMs in patients with stage IIB-IIIB SCLC who achieved complete remission (CR) after thoracic radio-chemotherapy.Methods:Clinical data of 191 patients with stage IIB-IIIB SCLC who achieved CR after thoracic radio-chemotherapy in Zhejiang Cancer Hospital from January 2009 to April 2016 were retrospectively analyzed. Common clinical factors related to the risk of BMs, including gender, age, thoracic radiotherapy dose, combined mode of radiotherapy and chemotherapy, pretreatment serum NSE and LDH, whether PCI was performed, TMN stage and PS score, were analyzed using log-rank method for univariate analysis, COX regression method for multivariate analysis and Kaplan-Meier method to plot the survival curve.Results:Univariate analysis showed that pretreatment LDH level≥240IU, pretreatment NSE ≥17 ng/ml and no PCI were positively correlated with the risk of BMs (all P＜0.05). Multivariate analysis showed that the risk of BMs was only positively correlated with pretreatment LDH≥240IU [HR: 1.90, 95%CI(1.07-3.37), P=0.029], and no PCI [HR:2.08, 95%CI(1.17-3.72), P=0.013]. Conclusion:Pretreatment serum LDH levels provide important value for predicting the risk of BMs in patients with stage IIB-IIIB SCLC who achieve CR after thoracic radio-chemotherapy.

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

Therapeutic Mechanism of Huangqi Guizhi Wuwutang on Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo reveal the mechanism of action of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis by pharmacological research based on its clinical application. MethodThe collagen-induced arthritis （CIA） rat model was established by injecting bovine type Ⅱ collagen and Freund's adjuvant at the tail， and was treated with different concentrations of Huangqi Guizhi Wuwutang. The rats were randomly divided into blank group， model group， methotrexate （0.9 mg·kg-1） group， and Huangqi Guizhi Wuwutang low- and high-dose （5.13， 20.52 g·kg-1·d-1） groups， with continuous intragastric administration for 4 weeks. The degree of joint swelling， weight， degree of foot swelling and arthritis index score were determined and the pathological changes of ankle joints were detected by hematoxylin and eosin （HE） staining to observe the therapeutic effect of Huangqi Guizhi Wuwutang on rheumatoid arthritis. In addition， enzyme-linked immunosorbent assay （ELISA） and Western blot were used to measure the expression of interleukin 1β （IL-1β）， interleukin 6 （IL-6）， interleukin 10 （IL-10） and tumor necrosis factor-α （TNF-α） in serum and the expression of nuclear factor kappa-B （NF-κB） pathway related proteins in synovial tissue， respectively to clarify the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis. ResultCompared with the conditions in blank group， the body weight and IL-10 level were decreased （P<0.01）， and the degree of foot swelling and arthritis index score， the levels of IL-1β， IL-6 and TNF-α， and the expression of NF-κB pathway related proteins were increased （P<0.01，） in the model group， with impaired morphology and function of the ankle joint. Additionally， compared with the model group， Huangqi Guizhi Wuwutang low- and high-dose groups had increased body weight of rats and IL-10 level （P<0.01）， and reduced degree of foot swelling and arthritis index score （P<0.05， P<0.01）， levels of IL-1β， IL-6 and TNF-α （P<0.01） and expression of NF-κB pathway related proteins （P<0.05， P<0.01）， with improved function and morphology of the ankle joint. ConclusionHuangqi Guizhi Wuwutang can significantly alleviate joint inflammatory injury by down-regulating NF-κB pathway and reducing the inflammatory response in CIA rats.