Mechanically skin-like and water-resistant self-healing bioelastomer for high-tension wound healing.

The biomedical application of self-healing materials in wet or (under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction of material-interface interactions. Rapid closure with uniform tension of high-tension wounds is often difficult, leading to further deterioration and scarring. Herein, a new type of thermosetting water-resistant self-healing bioelastomer (WRSHE) was designed by synergistically incorporating a stable polyglycerol sebacate (PGS) covalent crosslinking network and triple hybrid dynamic networks consisting of reversible disulfide metathesis (SS), and dimethylglyoxime urethane (Dou) and hydrogen bonds. And a resveratrol-loaded WRSHE (Res@WRSHE) was developed by a swelling, absorption, and crosslinked network locking strategy. WRSHEs exhibited skin-like mechanical properties in terms of nonlinear modulus behavior, biomimetic softness, high stretchability, and good elasticity, and they also achieved ultrafast and highly efficient self-healing in various liquid environments. For wound-healing applications of high-tension full-thickness skin defects, the convenient surface assembly by self-healing of WRSHEs provides uniform contraction stress to facilitate tight closure. Moreover, Res@WRSHEs gradually release resveratrol, which helps inflammatory response reduction, promotes blood vessel regeneration, and accelerates wound repair.

The catalytic triad of rice NARROW LEAF1 involves H234.

NARROW LEAF1 (NAL1) exerts a multifaceted influence on leaf morphology and crop yield. Recent crystal study proposed that histidine 233 (H233) is part of the catalytic triad. Here we report that unlike suggested previously, H234 instead of H233 is a component of the catalytic triad alongside residues D291 and S385 in NAL1. Remarkably, residue 233 unexpectedly plays a pivotal role in regulating NAL1's proteolytic activity. These findings establish a strong foundation for utilizing NAL1 in breeding programs aimed at improving crop yield.

An Encapsulation-Free and Hierarchical Porous Triboelectric Scaffold with Dynamic Hydrophilicity for Efficient Cartilage Regeneration.

Tissue engineering and electrotherapy are two promising methods to promote tissue repair. However, their integration remains an underexplored area, because their requirements on devices are usually distinct. Triboelectric nanogenerators (TENGs) have shown great potential to develop self-powered devices. However, due to their susceptibility to moisture, TENGs have to be encapsulated in vivo. Therefore, existing TENGs cannot be employed as tissue engineering scaffolds, which require direct interaction with surrounding cells. Here, the concept of triboelectric scaffolds (TESs) is proposed. Poly(glycerol sebacate), a biodegradable and relatively hydrophobic elastomer, is selected as the matrix of TESs. Each hydrophobic micropore in multi-hierarchical porous TESs efficiently serves as a moisture-resistant working unit of TENGs. Integration of tons of micropores ensures the electrotherapy ability of TESs in vivo without encapsulation. Originally hydrophobic TESs are degraded by surface erosion and transformed into hydrophilic surfaces, facilitating their role as tissue engineering scaffolds. Notably, TESs seeded with chondrocytes obtain dense and large matured cartilages after subcutaneous implantation in nude mice. Importantly, rabbits with osteochondral defects receiving TES implantation show favorable hyaline cartilage regeneration and complete cartilage healing. This work provides a promising electronic biomedical device and will inspire a series of new in vivo applications.

Structural insights into the N-terminal APHB domain of HrpA: mediating canonical and i-motif recognition.

RNA helicases function as versatile enzymes primarily responsible for remodeling RNA secondary structures and organizing ribonucleoprotein complexes. In our study, we conducted a systematic analysis of the helicase-related activities of Escherichia coli HrpA and presented the structures of both its apo form and its complex bound with both conventional and non-canonical DNAs. Our findings reveal that HrpA exhibits NTP hydrolysis activity and binds to ssDNA and ssRNA in distinct sequence-dependent manners. While the helicase core plays an essential role in unwinding RNA/RNA and RNA/DNA duplexes, the N-terminal extension in HrpA, consisting of three helices referred to as the APHB domain, is crucial for ssDNA binding and RNA/DNA duplex unwinding. Importantly, the APHB domain is implicated in binding to non-canonical DNA structures such as G-quadruplex and i-motif, and this report presents the first solved i-motif-helicase complex. This research not only provides comprehensive insights into the multifaceted roles of HrpA as an RNA helicase but also establishes a foundation for further investigations into the recognition and functional implications of i-motif DNA structures in various biological processes.

Identification of Additives in Disposable Face Masks and Evaluation of Their Toxicity Using Marine Medaka (Oryzias melastigma).

The COVID-19 pandemic has resulted in huge amounts of face masks worldwide. However, there is a lack of awareness on the additives and their potential risk to aquatic ecosystems of face masks. To address this issue, the additives and their toxicity in 13 face masks (e.g., polypropylene, polyethylene, and polylactic acid) were determined using nontarget analysis and bioassays. A total of 826 organic additives including intermediates (14.8%), surfactants (9.3%), plasticizers (8.2%), and antioxidants (6.1%) were tentatively identified, with 213 compounds being assigned confidence levels of 1 and 2. Interestingly, polylactic acid masks contained more additives than most polypropylene or polyethylene masks. Among these additives, the concentration of tris(2-ethylhexyl) phosphate in masks was 9.4-978.2 ng/g with a 100% detection frequency. Furthermore, 13 metals such as zinc (up to 202.0 µg/g), copper (32.5 µg/g), and chromium (up to 5.7 µg/g) were detected in the face masks. The methanol extracts of the masks showed the developmental toxicity, swimming behavior, and/or endocrine disruption in embryos/larvae of Oryzias melastigma. The findings demonstrate that face masks contain various toxic additives to marine medaka, which deserves close attention to pollution by face masks.

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.

Gelatin-modified 3D printed PGS elastic hierarchical porous scaffold for cartilage regeneration.

Regenerative cartilage replacements are increasingly required in clinical settings for various defect repairs, including bronchial cartilage deficiency, articular cartilage injury, and microtia reconstruction. Poly (glycerol sebacate) (PGS) is a widely used bioelastomer that has been developed for various regenerative medicine applications because of its excellent elasticity, biodegradability, and biocompatibility. However, because of inadequate active groups, strong hydrophobicity, and limited ink extrusion accuracy, 3D printed PGS scaffolds may cause insufficient bioactivity, inefficient cell inoculation, and inconsistent cellular composition, which seriously hinders its further cartilage regenerative application. Here, we combined 3D printed PGS frameworks with an encapsulated gelatin hydrogel to fabricate a PGS@Gel composite scaffold. PGS@Gel scaffolds have a controllable porous microstructure, with suitable pore sizes and enhanced hydrophilia, which could significantly promote the cells' penetration and adhesion for efficient chondrocyte inoculation. Furthermore, the outstanding elasticity and fatigue durability of the PGS framework enabled the regenerated cartilage built by the PGS@Gel scaffolds to resist the dynamic in vivo environment and maintain its original morphology. Importantly, PGS@Gel scaffolds increased the rate of cartilage regeneration concurrent with scaffold degradation. The scaffold was gradually degraded and integrated to form uniform, dense, and mature regenerated cartilage tissue with little scaffold residue.

Endocrine disruptor responses in the embryos of marine medaka (Oryzias melastigma) after exposure to aged plastic leachates.

The issue of the additives leached from plastics has attracted widespread attention. More crucially, endocrine disruptor status for several leached additives has been established. However, little is known about the overall endocrine disrupting effects of aged plastic leachates. Therefore, the transcriptional responses of endocrine-related genes were assessed in the embryos of marine medaka (Oryzias melastigma), which were exposed to the leachates from aged plastics that were immersed into the simulated seawater (SW) or fish digest (FD). The results revealed that there was a great difference between the SW and FD leachates in the transcripts of endocrine-related genes. With the exception of cyp1a, all target genes had their transcripts potentially down-regulated by the FD leachates. Chgl (a biomarker for estrogens), pparß (related to lipid metabolism), and cyp19a (related to sexual differentiation and reproduction) transcripts tended to be repressed by the SW leachates, while pparα, pparγ and cyp1a (mediating metabolism of xenobiotics) transcripts were stimulated. In addition, a redundancy analysis was carried out to determine the relationship between the leached additives and the transcriptional changes. However, the additives only partially explained the variation in the transcripts of endocrine-related genes (24.8%), indicating that other leached additives may have an impact on target gene transcription. This study provided molecular evidence of the aged plastic leachates' endocrine disrupting effects. Exploring the primary factors that affect the transcriptional alterations would require more research.

3D Printed Chondrogenic Functionalized PGS Bioactive Scaffold for Cartilage Regeneration.

Tissue engineering is emerging as a promising approach for cartilage regeneration and repair. Endowing scaffolds with cartilaginous bioactivity to obtain bionic microenvironment and regulating the matching of scaffold degradation and regeneration play a crucial role in cartilage regeneration. Poly(glycerol sebacate) (PGS) is a representative thermosetting bioelastomer known for its elasticity, biodegradability, and biocompatibility and is widely used in tissue engineering. However, the modification and drug loading of the PGS scaffold is still a key challenge due to its high temperature curing conditions and limited reactive groups, which seriously hinders its further functional application. Here, a simple versatile new strategy of super swelling-absorption and cross-linked networks locking is presented to successfully create the 3D printed PGS-CS/Gel scaffold for the first time based on FDA-approved PGS, gelatin (Gel) and chondroitin sulfate (CS). The PGS-CS/Gel scaffold exhibits the desirable synergistic properties of well-organized hierarchical structures, excellent elasticity, improved hydrophilicity, and cartilaginous bioactivity, which can promote the adhesion, proliferation, and migration of chondrocytes. Importantly, the rate of cartilage regeneration can be well-matched with degradation of PGS-CS/Gel scaffold, and achieve uniform and mature cartilage tissue without scaffold residual. The bioactive scaffold can successfully repair cartilage in a rabbit trochlear groove defect model indicating a promising prospect of clinical transformation.

Transcarotid versus transfemoral access for cerebrovascular intervention: protocol for a systematic review and meta-analysis.

INTRODUCTION: Cerebrovascular intervention is an excellent option to treat cerebrovascular diseases. Interventional access is a prerequisite and a foundation for cerebrovascular intervention, which is crucial to the success of an intervention. Although transfemoral arterial access (TFA) has become a popular and acceptable method of access for cerebrovascular angiography and intervention in clinical practice, it has some drawbacks that limit the usage in cerebrovascular interventions. Therefore, transcarotid arterial access (TCA) has been developed in cerebrovascular interventions. We aim to conduct a systematic review to compare the safety and efficacy of TCA with TFA for cerebrovascular intervention. METHODS AND ANALYSIS: In this protocol, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols were followed. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials will be searched mainly from 1 January 2004, to the formal search date. Additionally, reference lists and clinical trial registries will be searched. We will include clinical trials with more than 30 participants, which reported the endpoints of stroke, death and myocardial infarction. Two investigators will independently select studies, extract data and assess bias risk. A standardised mean difference with 95% CI will be presented for continuous data, and a risk ratio with 95% CI will be presented for dichotomous data. On inclusion of sufficient studies, subgroup analysis and sensitivity analysis will be conducted. The funnel plot and Egger's test will be used to assess publication bias. ETHICS AND DISSEMINATION: As only published sources will be used in this review, ethical approval is not required. We will publish the results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022316468.

Multifunctional Oxidized Dextran Cross-Linked Alkylated Chitosan/Drug-Loaded and Silver-Doped Mesoporous Bioactive Glass Cryogel for Hemostasis of Noncompressible Wounds.

Noncompressible wounds resulting from accidents and gunshots are typically associated with excessive bleeding, slow wound healing, and bacterial infection. Shape-memory cryogel presents great potential in controlling the hemorrhaging of noncompressible wounds. In this research, a shape-memory cryogel was prepared using a Schiff base reaction between alkylated chitosan (AC) and oxidized dextran (ODex) and then incorporated with a drug-laden and silver-doped mesoporous bioactive glass (MBG). Hydrophobic alkyl chains enhanced the hemostatic and antimicrobial efficiency of the chitosan, forming blood clots in the anticoagulated condition, and expanding the application scenarios of chitosan-based hemostats. The silver-doped MBG activated the endogenous coagulation pathway by releasing Ca2+ and prevented infection through the release of Ag+. In addition, the proangiogenic desferrioxamine (DFO) in the mesopores of the MBG was released gradually to promote wound healing. We demonstrated that AC/ODex/Ag-MBG DFO(AOM) cryogels exhibited excellent blood absorption capability, facilitating rapid shape recovery. It provided a higher hemostatic capacity in normal and heparin-treated rat-liver perforation-wound models than gelatin sponges and gauze. The AOM gels simultaneously promoted infiltration, angiogenesis, and tissue integration of liver parenchymal cells. Furthermore, the composite cryogel exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, AOM gels show great promise for clinical translation in treating lethal, noncompressible bleeding and the promotion of wound healing.

Preliminary Application Research of 3D Bioprinting in Craniofacial Reconstruction.

INTRODUCTION: In recent years, 3-dimensional (3D) printing has been widely used in regenerative medicine research and other fields because of its ability to customize macroscopic morphology and precisely control microstructure. Polymer scaffolds are 1 of the commonly used 3D bioprinting materials for defect repair and have recently been a research focus. Our article explored the bone-formation accelerating effect of 3D-printed porous scaffold Poly(glycerol sebacate) [PGS] in the critical bone defect of an enhancing rabbit mandibular model. Also, we overview and summarize the classification of 3D bioprinting materials and prospects for their various application scenarios in craniofacial reconstruction surgery. MATERIALS AND METHODS: A PGS elastomer scaffold was prepared by polymerizing equimolar amounts of sebacic acid and glycerol using a biological 3D printer. Six male New Zealand white rabbits were prepared (3 for the control group and 3 for the PGS group), each weighing 3 kg. Osteotomy was performed at the anterior edge of the ascending ramus of the mandible with a bone saw to open the 8 mm defect. Defects of the control group were empty, and defects of the PGS group were put into 8 mm-wide PGS elastomer scaffolds. The rabbits were euthanized 6 weeks after the operation, and the postoperative mandibles were collected. Information (presence or absence of pus from infection, nonunion, degree of macroscopic bone healing) was recorded, and the skeletal tissue was fixed in a paraformaldehyde solution. RESULTS: The mandible on the enhanced side was significantly longer than that on the opposite side, and the contralateral incisor was hyperplasia. The mandibles of rabbits in each group healed well, and there was no obvious local infection and purulence. The gross specimen appearance showed that both ends of the defect were connected. When comparing the reconstructed mandibles of the two groups, it is apparent that the width and thickness of the new bone in the PGS group were significantly better than that in the control group. CONCLUSIONS: This article verifies the effect of 3D polypore PGS scaffolds in animal craniomaxillofacial bone defects and introduces various application scenarios of 3D printing materials in craniomaxillofacial reconstruction surgery. There are quite good application prospects for 3D bioprinting in animal experiments and even clinical treatment of craniofacial defects.

Exposure to estrone disrupts the endocrine system of western mosquitofish (Gambusia affinis).

Estrone (E1) is one of the predominant natural estrogens detected in aquatic environments, yet little is known about its effects on the endocrine system in fish. In this study, the sex ratio, secondary sexual characteristics, gonadal histology, and transcriptional levels of genes closely related to sex differentiation and hypothalamic-pituitary-gonadal-liver (HPGL) axis were assessed in western mosquitofish (Gambusia affinis) after a full life-cycle exposure to E1 (0, 25.4, 143, 740, and 4300 ng/L) for 119 days. The results showed that exposure to 4300 ng/L of E1 resulted in 100% female and inhibited the growth of females. Exposure to environmentally relevant concentrations of E1 (143 and 740 ng/L) led to obvious feminization of skeletons and anal fins in males. Exposure to 740 and 4300 ng/L of E1 increased the proportion of mature spermatocytes in females, and exposure to 143 and 740 ng/L decreased the proportion of mature spermatocytes in males. Moreover, the transcripts of genes related to sex differentiation and HPGL axis were changed in the E1-exposed adult fish and embryos inside females. This study has provided valuable data on the endocrine disruption effects of E1 at environmentally relevant concentrations in G. affinis.

Toxicity and Estrogenicity of Bisphenol TMC in Oryzias melastigma via In Vivo and In Silico Studies.

Bisphenol 4-[1-(4-hydroxyphenyl)-3,3,5-trimethylcyclohexyl] phenol (BPTMC), as a substitute for bisphenol A, has been detected in environments. However, the ecotoxicological data of BPTMC are extremely scarce. Here, the lethality, developmental toxicity, locomotor behavior, and estrogenic activity of BPTMC at different concentrations (0.25-2000 µg/L) in marine medaka (Oryzias melastigma) embryos were examined. In addition, the in silico binding potentials of O. melastigma estrogen receptors (omEsrs) with BPTMC were assessed by docking study. Low-concentration BPTMC exposure (including an environmentally relevant concentration, 0.25 µg/L) resulted in stimulating effects, including hatching rate, heart rate, malformation rate, and swimming velocity. However, elevated concentrations of BPTMC led to an inflammatory response, changed heart rate and swimming velocity in the embryos and larvae. In the meantime, BPTMC (including 0.25 µg/L) altered the concentrations of estrogen receptor, vitellogenin, and endogenous 17 ß-estradiol as well as the transcriptional levels of estrogen-responsive genes in the embryos or/and larvae. Furthermore, elaborate tertiary structures of omEsrs were built by ab initio modeling, and BPTMC exerted potent binding potential with three omEsrs with -47.23, -49.23, and -50.30 kJ/mol for Esr1, Esr2a, and Esr2b, respectively. This work suggests that BPTMC has potent toxicity and estrogenic effects in O. melastigma.

A comparative study on endocrine disrupting effects of leachates from virgin and aged plastics under simulated media in marine medaka larvae (Oryzias melastigma).

Marine plastic pollution has garnered substantial attention, but the potential endocrine disrupting effects of plastic leachates in marine organisms remain unclear. In this study, the larvae of marine medaka (Oryzias melastigma) were exposed to the leachates from virgin and aged plastics soaked in simulated seawater and fish digest for 3 days. The concentrations of vitellogenin (VTG), estradiol (E2), and 11-ketotestosterone (11-KT), as well as the transcripts of endocrine-related genes were measured in the larvae. The results revealed that endogenous E2 was more sensitive to plastic leachates than VTG and 11-KT, which was significantly affected by 26.7 % of all plastic leachates. Among all genes, estrogen receptor α was impacted mostly, being up-regulated by 53.3 % of leachates from aged plastics. The comparative results demonstrated that the leachates from plastics with different statuses caused a greater difference than those from plastics in different simulated media, and the leachates from aged plastics resulted in higher endocrine disrupting effects than those from virgin plastics. In addition, seven leached additives (plasticizers and flame retardants) could explain 25.6 % of the hormonal effects using redundancy analysis, indicating that other additives in the plastic leachates can also play important roles in regulating the endocrine system of O. melastigma larvae.

Strong and Tough Supramolecular Covalent Adaptable Networks with Room-Temperature Closed-Loop Recyclability.

Development of closed-loop chemically recyclable plastics (CCRPs) that can be widely used in daily life can be a fundamental solution to the global plastic waste crisis. Hence, it is of great significance to develop easy-to-recycle CCRPs that possess superior or comparable material properties to the commodity plastics. Here, a novel dual crosslinked CCRP, namely, supramolecular covalent adaptable networks (supra-CANs), is reported, which not only displays mechanical properties higher than the strong and tough commodity polycarbonate, but also exhibits excellent solvent resistance as thermosets. The supra-CANs are constructed by introducing reversible noncovalent crosslinks into the dynamic covalent polymer networks, resulting in highly stiff and strong thermosets that also exhibit thermoplastic-like ductile and tough behaviors as well as reprocessability and rehealability. In great contrast, the analogs that do not have noncovalent crosslinks (CANs) show elastomeric properties with significantly decreased mechanical strength. Importantly, the developed supra-CANs and CANs can be converted back into the initial monomers in high yields and purity at room temperature, even with additives, which enables the sustainable polymer-monomer-polymer circulation. This work provides new design principles for high-performance chemically recyclable polymers as sustainable substitutes for the conventional plastics.

Ketamine modulates neural stem cell differentiation by regulating TRPC3 expression through the GSK3ß/ß-catenin pathway.

Ketamine, a popular anesthetic, is often abused by people for its hallucinogenic effect. Thus, the safety of ketamine in pediatric populations has been called into question for potential neurotoxic effects. However, ketamine also has neuroprotective effects in many brain injury models. The differentiation of neural stem cells (NSCs) was influenced significantly by ketamine, but the molecular mechanism is still unclear. NSCs were extracted from the hippocampi of postnatal day 1 rats and treated with ketamine to induce NSCs differentiation. Our results found that ketamine promoted neuronal differentiation of NSCs dose-dependently in a small dose range (P < 0.001). The main types of neurons from NSCs were cholinergic (51 ± 4 %; 95 % CI: 41-61 %) and glutamatergic neurons (34 ± 3 %; 95 % CI: 27-42 %). Furthermore, we performed RNA sequencing to promise a more comprehensive understanding of the molecules regulated by ketamine. Finally, we combined bioimaging and multiple molecular biology techniques to clarify that ketamine influences NSC differentiation by regulating transient receptor potential canonical 3 (TRPC3) expressions. Ketamine dramatically repressed TRPC3 expression (MD [95 % CI]=0.67 [0.40-0.95], P < 0.001) with a significant increase of phosphorylated glycogen synthase kinase 3ß (p-GSK3ß; MD [95 % CI]=1.00 [0.74-1.27], P < 0.001) and a decrease of ß-catenin protein expression (MD [95 % CI]=0.60 [0.32-0.89], P = 0.001), thereby promoting the differentiation of NSCs into neurons and inhibiting their differentiation into astrocytes. These results suggest that TRPC3 is necessary for ketamine to modulate NSC differentiation, which occurs partly via regulation of the GSK3ß/ß-catenin pathway.

Surviving the shift: College student satisfaction with emergency online learning during COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic disrupted education systems by forcing systems to shift to emergency online leaning. Online learning satisfaction affects academic achievement. Many factors affect online learning satisfaction. However there is little study focused on personal characteristics, mental status, and coping style when college students participated in emergency online courses. AIM: To assess factors related to satisfaction with emergency online learning among college students in Hebei province during the COVID-19 pandemic. METHODS: We conducted a cross-sectional survey of 1600 college students. The collected information included demographics, psychological aspects of emergent public health events, and coping style. Single factor, correlation, and multiple linear regression analyses were performed to identify factors that affected online learning satisfaction. RESULTS: Descriptive findings indicated that 62.9% (994/1580) of students were satisfied with online learning. Factors that had significant positive effects on online learning satisfaction were online learning at scheduled times, strong exercise intensity, good health, regular schedule, focusing on the epidemic less than one hour a day, and maintaining emotional stability. Positive coping styles were protective factors of online learning satisfaction. Risk factors for poor satisfaction were depression, neurasthenia, and negative coping style. CONCLUSION: College students with different personal characteristics, mental status, and coping style exhibited different degrees of online learning satisfaction. Our findings provide reference for educators, psychologists, and school administrators to conduct health education intervention of college students during emergency online learning.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice / 中华放射医学与防护杂志

Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.