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Objectives Perianal infection is a serious complication in patients undergoing chemotherapy for haematological malignancies. Therefore, we aimed to develop a predictive model to help medical staff promptly screen patients at a high risk of perianal infection during chemotherapy.Design This was a single-centre prospective observational study.Setting This study was conducted in a tertiary teaching hospital in Chengdu, China.Participants The study sample comprised 850 patients with haematological malignancies who underwent chemotherapy at the department of haematology or our hospital between January 2021 and June 2022.Interventions The included patients were randomly divided into training and validation groups in a 7:3 ratio. Based on the discharge diagnosis, patients with perianal infection were selected as the case group and the other patients were selected as the control group.Outcome measure The main outcome measure was the occurrence of perianal infections.Results A predictive model for perianal infections was established. A history of perianal infection, haemorrhoids, constipation and duration of diarrhoea were independent risk factors. The area under the curve of the The area under the receiver operating characteristic (ROC) curve for the training and validation groups were 0.784 (95% CI 0.727 to 0.841) and 0.789 (95% CI 0.818 to 0.885), respectively. Additionally, the model had good calibration in both the training and validation groups with a non-significant Hosmer-Lemeshow test (p=0.999 and 0.482, respectively).Conclusions The risk prediction model, including a history of perianal infection, history of haemorrhoids, constipation and duration of diarrhoea ≥3 days of perianal infection in patients with haematological malignancies during chemotherapy, has good prediction reliability and can be helpful in guiding clinical medical staff in screening and early intervention of high-risk groups.

BackgroundThe topic of minimal residual disease (MRD) has emerged as a crucial subject matter in the domain of oncology in recent years. The detection and monitoring of MRD have become essential for the diagnosis, treatment, and prognosis of various types of malignancy.AimsThe purpose of this study is to explore the research trends, hotspots, and frontiers of MRD in the last two decades through bibliometric analysis.MethodsWe employed Web of Science databases to carry out a bibliometric visualization analysis of research on 8,913 academic papers about MRD research from 2002 to 2022. VOSviewer, CiteSpace, RStudio, and a bibliometric online analysis platform were mainly used to conduct co-occurrence analysis and cooperative relationship analysis of countries/regions, institutions, journals, and authors in the literature. Furthermore, co-occurrence, co-citation, and burst analyses of keyword and reference were also conducted to generate relevant knowledge maps.ResultsIn the past 20 years, the number of MRD research papers has presented an overall rising trend, going through three stages: a plateau, development, and an explosion. The output of articles in the United States was notably superior and plays a dominant role in this field, and the Netherlands had the highest average citation per article. The most productive and influential institution was the University of Texas MD Anderson Cancer Center. Blood published the most papers and was the most cited journal. A collection of leading academics has come to the fore in the research field, the most prolific of which is Kantarjian HM. It was found that the application of MRD in “acute myeloid leukemia”, “acute lymphoblastic leukemia”, “multiple myeloma”, as well as the detection technology of MRD, are the research hotspots and frontiers in this domain. Furthermore, we analyzed the co-citation network of references and found that the top 10 co-cited references were all associated with MRD in hematological malignancies.ConclusionThis bibliometric visualization analysis conducted a thorough exploration into the research hotspots and trends in MRD from 2002 to 2022. Our findings can aid researchers in recognizing possible collaborations, guiding future research directions, and fostering the growth of MRD detection and monitoring technologies.

Abstract KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates. Mechanistically, it is found that KMT2D deficiency leads to the activation of the mTOR pathway in both mouse and human AML cells. Kmt2d directly regulates the expression of Ddit4, a negative regulator of the mTOR pathway. Consistent with the abnormal ribosome biogenesis, it is shown that CX‐5461, an inhibitor of RNA polymerase I, significantly restrains the growth of AML with Kmt2d loss in vivo and extends the survival of leukemic mice. These studies validate KMT2D as a de facto tumor suppressor in AML and reveal an unprecedented vulnerability to ribosome biogenesis inhibition.

BackgroundIn recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens’ distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs.MethodsIn this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram.ResultsAmong 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin

BackgroundThe overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.MethodsThe prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.ResultsFor untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% CI, 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% CI, 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients (P = 0.02). In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% CI, 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.ConclusionThis meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.

The technology of infrared dim- and small-target detection is irreplaceable in many fields, such as those of missile early warning systems and forest fire prevention, among others. However, numerous components interfere with infrared imaging, presenting challenges for achieving successful detection of infrared dim and small targets with a low rate of false alarms. Hence, we propose a new infrared dim- and small-target detection network, Multiscale Feature Extraction U-Net for Infrared Dim- and Small-Target Detection (MFEU-Net), which can accurately detect targets in complex backgrounds. It uses the U-Net structure, and the encoders and decoders consist of ReSidual U-block and Inception, allowing rich multiscale feature information to be extracted. Thus, the effectiveness of algorithms in detecting very small-sized targets can be improved. In addition, through the multidimensional channel and spatial attention mechanism, the model can be adjusted to focus more on the target area in the image, improving its extraction of target information and detection performance in different scenarios. The experimental results show that our proposed algorithm outperforms other advanced algorithms in detection performance. On the MFIRST, SIRST, and IRSTD-1k datasets, we achieved detection rates of 0.864, 0.962, and 0.965; IoU values of 0.514, 0.671, and 0.630; and false alarm rates of 3.08 × 10−5, 2.61 × 10−6, and 1.81 × 10−5, respectively.

Infrared and visible remote sensing image registration is significant for utilizing remote sensing images to obtain scene information. However, it is difficult to establish a large number of correct matches due to the difficulty in obtaining similarity metrics due to the presence of radiation variation between heterogeneous sensors, which is caused by different imaging principles. In addition, the existence of sparse textures in infrared images as well as in some scenes and the small number of relevant trainable datasets also hinder the development of this field. Therefore, we combined data-driven and knowledge-driven methods to propose a Radiation-variation Insensitive, Zero-shot learning-based Registration (RIZER). First, RIZER, as a whole, adopts a detector-free coarse-to-fine registration framework, and the data-driven methods use a Transformer based on zero-shot learning. Next, the knowledge-driven methods are embodied in the coarse-level matches, where we adopt the strategy of seeking reliability by introducing the HNSW algorithm and employing a priori knowledge of local geometric soft constraints. Then, we simulate the matching strategy of the human eye to transform the matching problem into a model-fitting problem and employ a multi-constrained incremental matching approach. Finally, after fine-level coordinate fine tuning, we propose an outlier culling algorithm that only requires very few iterations. Meanwhile, we propose a multi-scene infrared and visible remote sensing image registration dataset. After testing, RIZER achieved a correct matching rate of 99.55% with an RMSE of 1.36 and had an advantage in the number of correct matches, as well as a good generalization ability for other multimodal images, achieving the best results when compared to some traditional and state-of-the-art multimodal registration algorithms.

Abstract Background Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. Methods Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). Results Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1–34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7–8.8 months). The median overall survival was 24.3 months (95% CI 14.4–41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. Conclusions Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. Trial registration The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was −10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n = 125] or MESA [n = 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9–93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8–91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, −5.6–10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

BackgroundMeningioma is a common type of intracranial tumor in adults. It rarely arises in the chest, with only a few case reports in the English literature. Here, we report the case of a patient with a primary ectopic meningioma (PEM) located in the thoracic cavity.Case presentationA 55-year-old woman presented with exercise-induced asthma, chest tightness, intermittent dry cough and fatigue for several months. Computed tomography revealed the presence of a huge mass in the thoracic cavity, with no connection to the spinal canal. Lung cancer and mesothelioma were suspected, and surgery was performed. Grossly, the mass was a grayish-white solid 9.5 cm × 8.4 cm × 5.3 cm in size. The microscopic morphology of the lesion was consistent with that of typical central nervous system meningioma. The pathological subtype was transitional meningioma. The tumor cells were arranged in a fascicular, whorled, storiform and meningithelial pattern, with occasional intranuclear pseudo-inclusions and psammoma bodies. In focal areas tumor cells were considerably dense, and the cells were round or irregular in shape, with less cytoplasm, uniform nuclear chromatin, and visible nucleoli and mitoses (2/10 HPF). By immunohistochemistry, the neoplastic cells showed strong and diffuse staining with vimentin, epithelial membrane antigen and SSTR2 with variable expression of PR, ALK and S100 protein. However, the cells were negative for GFAP, SOX-10, inhibin, CD34, STAT6, smooth muscle actin, desmin, CKpan, D2-40, WT-1, CK5/6 and CD45. The highest proliferation index by Ki-67 was 15%. The abnormal expression of ALK led to the initial misdiagnosis of an inflammatory myofibroblastic tumor. After 12 months of follow-up, no disease progression was observed.ConclusionThe presence of primary ectopic meningiomas in the thoracic cavity is extremely rare, and this tumor is easily misdiagnosed clinically. Imaging is suggested to determine the location and possible differential diagnosis, while the final diagnosis should be via pathological examination. Immunohistochemistry is crucial for disease diagnosis. Owing to our limited knowledge of PEM, its pathogenesis and tissue of origin remain unclear. Clinicians should pay close attention to such potential patients. The present case report may provide insights into the diagnosis and therapy of patients with this tumor.

In recent years, growing emphasis has been placed on amino acids and their role in hematologic malignancies. Cancer cell metabolism is altered during tumorigenesis and development to meet expanding energetic and biosynthetic demands. Amino acids not only act as energy-supplying substances, but also play a vital role via regulating key signaling pathways, modulating epigenetic factors and remodeling tumor microenvironment. Targeting amino acids may be an effective therapeutic approach to address the current therapeutic challenges. Here, we provide an updated overview of mechanisms by which amino acids facilitate tumor development and therapy resistance. We also summarize novel therapies targeting amino acids, focusing on recent advances in basic research and their potential clinical implications.

BackgroundThe prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT).MethodsPatients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen’s safety. The survival curve was estimated via the Kaplan-Meier method.ResultsTwenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8–13 days) and 13 days (9–31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable.ConclusionsChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.

The role of enhancer variants in hepatocellular carcinoma (HCC) predisposition remains unknown. Here, the authors perform a genome-wide survey of HCC-susceptible enhancer variants in 11,958 individuals, identify rs73613962 within the intronic region of PRMT7 and find that PRMT7 upregulation predisposes to HCC.

Abstract Janus kinase 2 (JAK2) hyperactivation by JAK2 V617F mutation leads to myeloproliferative neoplasms (MPNs) and targeting JAK2 could serve as a promising therapeutic strategy for MPNs. Here, we report that Flonoltinib Maleate (FM), a selective JAK2/FLT3 inhibitor, shows high selectivity for JAK2 over the JAK family. Surface plasmon resonance assays verified that FM had a stronger affinity for the pseudokinase domain JH2 than JH1 of JAK2 and had an inhibitory effect on JAK2 JH2V617F. The cocrystal structure confirmed that FM could stably bind to JAK2 JH2, and FM suppressed endogenous colony formation of primary erythroid progenitor cells from patients with MPNs. In several JAK2 V617F-induced MPN murine models, FM could dose-dependently reduce hepatosplenomegaly and prolong survival. Similar results were observed in JAK2 V617F bone marrow transplantation mice. FM exhibited strong inhibitory effects on fibrosis of the spleen and bone marrow. Long-term FM treatment showed good pharmacokinetic/pharmacodynamic characteristics with high drug exposure in tumor-bearing tissues and low toxicity. Currently, FM has been approved by the National Medical Products Administration of China (CXHL2000628), and this study will guide clinical trials for patients with MPNs.

Inducing senescence in cancer cells is an emerging strategy for cancer therapy. The dysregulation and mutation of genes encoding cyclin‐dependent kinases (CDKs) have been implicated in various human cancers. However, whether CDK can induce cancer cell senescence remains poorly understood. We observed that CDK16 expression was high in multiple cancer types, including lung cancer, whereas various replicative senescence models displayed low CDK16 expression. CDK16 knockdown caused senescence‐associated phenotypes in lung cancer cell lines. Interestingly, the CDK16 3′ UTR was shortened in cancer and lengthened in senescence models, which was regulated by alternative polyadenylation (APA). The longer 3′UTR [using the distal polyA (pA) site] generated less protein than the shorter one (using the proximal pA site). Since microRNAs (miRNAs) usually bind to the 3′UTR of target genes to suppress their expression, we investigated whether miRNAs targeting the region between the shortened and longer 3′UTR are responsible for the reduced expression. We found that miR‐485‐5p targeted the 3′UTR between the distal and proximal pA site and caused senescence‐associated phenotypes by reducing protein production from the longer CDK16 transcript. Of note, CDK16 knockdown led to a reduced expression of MYC proto‐oncogene, bHLH transcription factor (MYC) and CD274 molecule (PD‐L1), which in turn enhanced the tumor‐suppressive effects of senescent cancer cells. The present study discovered that CDK16, whose expression is under the regulation of APA and miR‐485‐5p, is a potential target for prosenescence therapy for lung cancer.

The Plio-Pleistocene colobines Paracolobus chemeroni and Paracolobus mutiwa were larger than any extant monkey, overlapping with chimpanzees in body size. These species are now known from partial skeletons (KNM-BC3 and KNM-WT16827) providing the first opportunity to assess and compare their locomotor behavior. To date, none of P. mutiwa and only the forelimb of P. chemeroni have been examined. We conducted a functional analysis of the hip and thigh of these specimens to assess patterns of hindlimb use. The hipbones and femora of the Paracolobus skeletons are compared to those of over 150 extant colobines and cercopithecines, as well as those of the large-bodied fossil colobine Cercopithcoides williamsi and cercopithecine Theropithecus oswaldi. Model II (reduced major axis) regression is used to examine pelvic and femoral dimensions in an allometric context, using femoral head size as an estimator of body mass. The two Paracolobus species exhibit morphologies suggesting differing levels of emphasis on terrestrial and arboreal behaviors. Although it is a colobine, P. mutiwa, like C. williamsi and T. oswaldi, possesses cercopithecine-like features, including a tall greater trochanter, low femoral neck-shaft angle, and long lower iliac height, indicating an emphasis on a terrestrial locomotor habit. P. chemeroni, on the other hand, more closely resembles the extant colobines in these morphologies. However, analysis of ischial length reveals that P. chemeroni deviates from the colobines and clusters with the cercopithecines. Our results suggest that, although they are congeneric, P. chemeroni and P. mutiwa not only differed in their locomotor specializations, but both of their locomotor repertoires were unlike that of any extant monkey.

Under low-illumination conditions, the quality of the images collected by the sensor is significantly impacted, and the images have visual problems such as noise, artifacts, and brightness reduction. Therefore, this paper proposes an effective network based on Retinex for low-illumination image enhancement. Inspired by Retinex theory, images are decomposed into two parts in the decomposition network, and sent to the sub-network for processing. The reconstruction network constructs global and local residual convolution blocks to denoize the reflection component. The enhancement network uses frequency information, combined with attention mechanism and residual density network to enhance contrast and improve the details of the illumination component. A large number of experiments on public datasets show that our method is superior to existing methods in both quantitative and visual aspects.

Abstract Drug-resistance is a major problem preventing a cure in patients with multiple myeloma (MM). Previously, we demonstrated that activated-leukocyte-cell-adhesion-molecule (ALCAM) is a prognostic factor in MM and inhibits EGF/EGFR-initiated MM clonogenicity. In this study, we further showed that the ALCAM-EGF/EGFR axis regulated the MM side population (SP)-mediated drug-resistance. ALCAM-knockdown MM cells displayed an enhanced ratio of SP cells in the presence of bone marrow stromal cells (BMSCs) or with the supplement of recombinant EGF. SP MM cells were resistant to chemotherapeutics melphalan or bortezomib. Drug treatment stimulated SP-genesis. Mechanistically, EGFR, primed with EGF, activated the hedgehog pathway and promoted the SP ratio; meanwhile, ALCAM inhibited EGFR downstream pro-MM cell signaling. Further, SP MM cells exhibited an increased number of mitochondria compared to the main population. Interference of the mitochondria function strongly inhibited SP-genesis. Animal studies showed that combination therapy with both an anti-MM agent and EGFR inhibitor gefitinib achieved prolonged MM-bearing mice survival. Hence, our work identifies ALCAM as a novel negative regulator of MM drug-resistance, and EGFR inhibitors may be used to improve MM therapeutic efficacy.

BackgroundPost-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are both common graft-versus-host disease (GVHD) prophylaxis strategies in allo-HSCT from unrelated donors. However, no consensus has reached on which regimen is optimal. Although several studies concerning this topic exist, the outcomes of different studies still conflict with each other. Therefore, an overall comparison of the two regimens is urgently needed to help make informed clinical decisions.MethodsStudies comparing PTCy and ATG regimens in unrelated donor (UD) allo-HSCT were searched in four critical medical databases from inception to April 17, 2022. The primary outcome was grade II-IV aGVHD, grade III-IV aGVHD and chronic GVHD (cGVHD), and the secondary outcomes included overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), and several severe infectious complications. The quality of articles was assessed by the Newcastle-Ottawa scale (NOS), and data were extracted by two independent investigators and then analyzed by RevMan 5.4.ResultsSix out of 1091 articles were eligible for this meta-analysis. Compared with the ATG regimen, prophylaxis based on PTCy achieved a lower incidence of grade II-IV aGVHD incidence (RR=0.68, 95% CI 0.50-0.93, P=0.010, I2 = 67%), grade III-IV aGVHD (RR=0.32, 95% CI 0.14-0.76, P=0.001, I2 = 75%), NRM (RR=0.67, 95% CI 0.53-0.84, P=0.17, I2 = 36%), EBV-related PTLD (RR=0.23, 95% CI 0.09-0.58, P=0.85, I2 = 0%) and better OS (RR=1.29, 95% CI 1.03-1.62, P=0.0001, I2 = 80%). The cGVHD, RI, CMV reactivation and BKV-related HC showed no significant difference between the two groups (RR=0.66, 95% CI 0.35-1.26, P

With the widespread use of smartphones, many people spend much time on smartphones for shopping, learning, socializing, and so on, which can affect an individual's mental health and work performance. Especially, individual perceived conflict at work may increase their social anxiety and thus raise the risk of their smartphone addiction. This study collected data from 577 corporate employees in China through convenience sampling to explain the influence mechanism of work conflict on smartphone addiction and to verify the moderating role of rumination. Statistical results show that relationship conflicts, task conflicts, and process conflicts positively affect smartphone addiction by enhancing social anxiety. Moreover, rumination positively moderates the relationship between work conflict and smartphone addiction. People with high rumination are more likely to escape reality due to conflict at work, which further enhances their smartphone addiction behaviors. Our study suggests that a relatively harmonious working atmosphere should be established within organizations, especially for employees with rumination. Work conflict is a predisposing factor for social anxiety and smartphone addiction in individuals with high rumination.

In eukaryotes, alternative promoter (AP), alternative splicing (AS), and alternative polyadenylation (APA) are three crucial regulatory mechanisms that modulate message RNA (mRNA) diversity. Although AP, AS and APA are involved in diverse biological processess, whether they have dynamic changes in Angiotensin II (Ang II) induced senescence in rat primary aortic endothelial cells (RAECs), an important cellular model for studying cardiovascular disease, remains unclear. Here we integrated both PacBio single-molecule long-read isoform sequencing (Iso-Seq) and Illumina short-read RNA sequencing (RNA-seq) to analyze the changes of AP, AS and APA in Ang II-induced senescent RAECs. Iso-Seq generated 36,278 isoforms from 10,145 gene loci and 65.81% of these isoforms are novel, which were further cross-validated by public data obtained by other techonologies such as CAGE, PolyA-Seq and 3′READS. APA contributed most to novel isoforms, followed by AS and AP. Further investigation showed that AP, AS and APA could all contribute to the regulation of isoform, but AS has more dynamic changes compared to AP and APA upon Ang II stimulation. Genes undergoing AP, AS and APA in Ang II-treated cells are enriched in various pathways related to aging or senescence, suggesting that these molecular changes are involved in functional alterations during Ang II-induced senescence. Together, the present study largely improved the annotation of rat genome and revealed gene expression changes at isoform level, extending the understanding of the complexity of gene regulation in Ang II-treated RAECs, and also provided novel clues for discovering the regulatory mechanism undelying Ang II caused vascular senescence and diseases.

Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China.Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the “HemaTank” Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition.Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%–56.8%) than MM without ASCT (range 49.1%–64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment.Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.

BackgroundDuvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types.MethodsWe searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed.ResultsWe included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%).ConclusionGenerally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.

Introduction: Venlafaxine is one of the most commonly used anti-depressant and antineoplastic drug. Previous studies have predicted venlafaxine as an anti-cancer compound, but the therapeutic effects of venlafaxine in melanoma have not yet been demonstrated. Nur77 is an orphan nuclear receptor that highly expressed in melanoma cells and can interact with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic protein.Method: We examined the effects of venlafaxine in MV3 cells in vitro and MV3 xenograft tumor in nude mice. Western-blot, PCR, TUNEL assay and immunofluorescence were used to reveal the growth of melanoma cells.Results: Here, our data revealed that venlafaxine could reduce the growth, and induce apoptosis of melanoma cells through a Nur77-dependent way. Our results also showed that treatment with venlafaxine (20 mg/kg, i.p.) potently inhibited the growth of melanoma cells in nude mice. Mechanistically, venlafaxine activated JNK1/2 signaling, induced Nur77 expressions and mitochondrial localization, thereby promoting apoptosis of melanoma cells. Knockdown of Nur77 and JNK1/2, or inhibition of JNK1/2 signaling with its inhibitor SP600125 attenuated the anti-cancer effects of venlafaxine.Conclusion: In summary, our results suggested venlafaxine as a potential therapy for melanoma.

Abstract Background Colorectal cancer is a malignant gastrointestinal cancer, in which some advanced patients would develop cancer cachexia (CAC). CAC is defined as a multi-factorial syndrome characterized by weight loss and muscle loss (with or without fat mass), leading to progressive dysfunction, thereby increasing morbidity and mortality. ApcMin/+ mice develop spontaneous intestinal adenoma, which provides an established model of colorectal cancer for CAC study. Upon studying the ApcMin/+ mouse model, we observed a marked decrease in weight gain beginning around week 15. Such a reduction in weight gain was rescued when ApcMin/+ mice were crossed with MMP12−/− mice, indicating that MMP12 has a role in age-related ApcMin/+-associated weight loss. As a control, the weight of MMP12−/− mice on a weekly basis, their weight were not significantly different from those of WT mice. Methods ApcMin/+; MMP12−/− mice were obtained by crossing ApcMin/+ mice with MMP12 knockout (MMP12 −/−) mice. Histological scores were assessed using hematoxylin-eosin (H&E) staining. MMP12 expression was confirmed by immunohistochemistry and immunofluorescence staining. ELISA, protein microarrays and quantitative Polymerase Chain Reaction (qPCR) were used to investigate whether tumor could up-regulate IL-6. Cell-based assays and western blot were used to verify the regulatory relationship between IL-6 and MMP12. Fluorescence intensity was measured to determine whether MMP12 is associated with insulin and insulin-like growth factor 1 (IGF-1) in vitro. MMP12 inhibitors were used to explore whether MMP12 could affect the body weight of ApcMin/+ mice. Results MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area (all mice had C57BL/6 background) in ApcMin/+ mice, while inhibiting MMP12 could suppress weight loss in ApcMin/+ mice. MMP12 was up-regulated in muscle tissues and peritoneal macrophages of ApcMin/+ mice. IL-6 in tumor cells and colorectal cancer patients is up-regulation. IL-6 stimulated MMP12 secretion of macrophage. Conclusions MMP12 is essential for controlling body weight of Apc Min/+ mice. Our study shows that it exists the crosstalk between cancer cells and macrophages in muscle tissues that tumor cells secrete IL-6 inducing macrophages to up-regulate MMP12. This study may provide a new perspective of MMP12 in the treatment for weight loss induced by CAC.

BackgroundAmino acid (AA) metabolism plays a crucial role in cancer. However, its role in acute myeloid leukemia (AML) is still unavailable. We screened out AA metabolic genes, which related to prognosis, and analyzed their correlation with tumor immune microenvironment in AML.MethodsWe evaluated 472 amino acid metabolism-related genes in 132 AML patients. The predictive risk model was developed according to differentially expressed genes, univariate Cox and LASSO analyses. We validated the risk signature by survival analysis and independence tests. Single-sample gene set enrichment analysis (ssGSEA), tumor immune microenvironment (TME), tumor mutation burden (TMB), functional enrichment, and the IC50 of drugs were assessed to explore the correlations among the risk model, immunity, and drug sensitivity of AML.ResultsSix amino acid metabolism-related genes were confirmed to develop the risk model, including TRH, HNMT, TFEB, SDSL, SLC43A2, and SFXN3. The high-risk subgroup had an immune “hot” phenotype and was related to a poor prognosis. The high-risk group was also associated with more activity of immune cells, such as Tregs, had higher expression of some immune checkpoints, including PD1 and CTLA4, and might be more susceptible to immunotherapy. Xenobiotic metabolism, the reactive oxygen species (ROS) pathway, fatty acid metabolism, JAK/STAT3, and the inflammatory response were active in the high-risk subgroup. Furthermore, the high-risk subgroup was sensitive to sorafenib, selumetinib, and entospletinib. ssGSEA discovered that the processes of glutamine, arginine, tryptophan, cysteine, histidine, L-serine, isoleucine, threonine, tyrosine, and L-phenylalanine metabolism were more active in the high-risk subgroup.ConclusionThis study revealed that AA metabolism-related genes were correlated with the immune microenvironment of AML patients and could predict the prognosis and immunotherapy response of AML patients.

ObjectivesLittle is known about the effects and the extent that childhood adversity has on post-traumatic stress disorder (PTSD) and depression.Study designA population-based, epidemiological study from the Wenchuan earthquake.MethodsA total of 5,195 Wenchuan Earthquake adolescent survivors aged 11–18 years from nine high schools in southwest China completed questionnaires that assessed their PTSD and depression symptoms due to childhood maltreatment, stressful life events, and childhood earthquake exposure.ResultsThe PTSD and depression prevalences were 7.1 and 32.4%. After controlling for age and gender, the multiple linear regressions revealed that stressful life events had the most significant direct effect on depression (β = 0.491), followed by childhood emotional abuse (β = 0.085), and earthquake exposure (β = 0.077). Similarly, stressful life events (β = 0.583) were found to have more significant direct effects on PSTD, followed by earthquake exposure (β = 0.140); however, childhood emotional abuse was not found to have an effect. The structural equation modeling (SEM) revealed that there were interactions between the three childhood adversities, with all three concurrently affecting both PTSD and depression.ConclusionThese findings add weight to the supposition that psychological maltreatment, negative life events, and earthquake exposure contribute to PTSD and depression. In particular, the identification of subgroups that have a high prevalence of these childhood adversities could assist professionals to target populations that are at high risk of mental health problems.

ObjectiveThis study examined whether sleep disturbance was a mediator between alexithymic traits and post-traumatic stress disorder (PTSD) COVID-19 pandemic-related stress symptoms, and explored whether self-esteem moderated the alexithymic contribution to poor sleep and PTSD symptoms.MethodA representative sample of young adults (N = 2,485) from six universities in Southwest China completed online self-report surveys on alexithymia, sleep, PTSD, self-esteem, sociodemographic information, and health-related behaviors.ResultsHigh alexithymic young adults were found to be more likely to have higher sleep problems and higher PTSD symptoms. The moderated mediation model showed that sleep problems mediated the associations between alexithymia and PTSD symptoms. Alexithymic people with lower self-esteem were more likely to have elevated PTSD symptoms and sleep problems than those with higher self-esteem.ConclusionTargeted psychological interventions for young people who have difficulty expressing and identifying emotions are recommended as these could assist in reducing their post-traumatic psychophysical and psychological problems. Improving self-esteem could also offer some protection for trauma-exposed individuals.

BackgroundCopanlisib is an intravenously administered pan-class I PI3K inhibitor that has been demonstrated to have appreciable effects in the treatment of patients with lymphoma. The purpose of this meta-analysis was to evaluate the efficacy and safety of copanlisib for treating patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).MethodsPubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published prior to July 2022. The efficacy evaluation included complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), overall response rate (ORR), disease control rate (DCR), rate of progressive disease (PDR), median progression-free survival (PFS), and median overall survival (OS). Any grade adverse events (AEs) and grade ≥3 AEs were synthesized to assess its safety.ResultsEight studies with a total of 652 patients with R/R B-NHL were identified. The pooled CR, PR, ORR, SDR, DCR, and PDR from all 8 articles were 13%, 40%, 57%, 19%, 86%, and 9%, respectively. The CR and ORR of combination therapy with rituximab were higher than those with copanlisib monotherapy for R/R B-NHL (34% vs. 6%, p

The proteasome inhibitors (PIs) bortezomib and carfilzomib, which target proteasome 20S subunit beta 5 (PSMB5) in cells, are widely used in multiple myeloma (MM) treatment. In this study, we demonstrated the role of interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2) in MM PI resistance. Gain- and loss-of-function studies showed that ISG20L2 suppressed MM cell sensitivity to PIs in vitro and in vivo. Patients with ISG20L2lo MM had a better response to PIs and a longer overall survival than patients with ISG20L2hi MM. Biotinylated bortezomib pull-down assays showed that ISG20L2 competed with PSMB5 in binding to bortezomib. The surface plasmon resonance assay confirmed the direct binding of bortezomib to ISG20L2. In ISG20L2hi MM cells, ISG20L2 attenuated the binding of bortezomib to PSMB5, resulting in lower inhibition of proteasome activity and therefore less bortezomib-induced cell death. Overall, we identified a potentially novel mechanism by which ISG20L2 conferred bortezomib resistance on MM. The expression of ISG20L2 correlated with MM PI responses and patient treatment outcomes.

Visual object trackers based on Siamese networks perform well in visual object tracking (VOT); however, degradation of the tracking accuracy occurs when the target has fast motion, large-scale changes, and occlusion. In this study, in order to solve this problem and enhance the inference speed of the tracker, fast and accurate visual tracking with a group convolution and pixel-level correlation based on a Siamese network is proposed. The algorithm incorporates multi-layer feature information on the basis of Siamese networks. We designed a multi-scale feature aggregated channel attention block (MCA) and a global-to-local-information-fused spatial attention block (GSA), which enhance the feature extraction capability of the network. The use of a pixel-level mutual correlation operation in the network to match the search region with the template region refines the bounding box and reduces background interference. Comparing our work with the latest algorithms, the precision and success rates on the UAV123, OTB100, LaSOT, and GOT10K datasets were improved, and our tracker was able to run at 40FPS, with a better performance in complex scenes such as those with occlusion, illumination changes, and fast-motion situations.

With the rapid development of science and technology, high-resolution remote sensing cameras are now widely used in various fields. At the beginning of camera attitude adjustment, residual torque due to state changes can affect platform stability and lead to the degradation of imaging quality. This paper analyzes the effect of external disturbances on the attitude of the satellite platform according to the Newton–Euler method. In order to effectively realize the self-balancing of the torque of the remote sensing camera rotary table and eliminate the influence of the residual torque on the stability of the satellite platform, this study designs a torque balancing mechanism for the two-axis rotary table of a remote sensing camera based on the first-generation balancing mechanism. Firstly, this paper provides a detailed analysis of the mechanism equilibrium principle from the theoretical point of view based on the theories related to momentum moment theorem and momentum moment conservation law. Then, the dynamics model of the torque balancing mechanism is built, and the dynamics simulation analysis is carried out in this paper. The analysis results show that compared with the first-generation torque balancing mechanism, the residual torque of the second-generation torque balancing mechanism is reduced by 66.67%, the peak value of the residual torque is reduced by 57.55%, the mass of the balancing flywheel is reduced by 74.14%, and the torque balancing time is reduced by 42.86%. Finally, two torque balancing mechanism prototypes were fabricated at equal scale for test verification in this paper. The test results show that compared with the first-generation torque balancing mechanism, the residual torque of the second-generation test prototype is reduced by 40%, the peak of the residual torque is reduced by 25%, the mass of the balancing flywheel is reduced by 60.34%, and the torque balancing time is reduced by 51.06%. There are some differences between the simulation analysis and the experimental results, but the overall trend is consistent with the theory. Through theoretical derivation, simulation analysis and experimental verification, the correctness and feasibility of the proposed second-generation torque balancing mechanism are fully confirmed, which has certain reference significance and engineering application value for the torque self-balancing scheme of rotary tables.

The non-uniformity of infrared detectors’ readout circuits can lead to stripe noise in infrared images, which affects their effective information and poses challenges for subsequent applications. Traditional denoising algorithms have limited effectiveness in maintaining effective information. This paper proposes a multi-level image decomposition method based on an improved LatLRR (MIDILatLRR). By utilizing the global low-rank structural characteristics of stripe noise, the noise and smooth information are decomposed into low-rank part images, and texture information is adaptively decomposed into several salient part images, thereby better preserving texture edge information in the image. Sparse terms are constructed according to the smoothness of the effective information in the final low-rank part of the image and the sparsity of the stripe noise direction. The modeling of stripe noise is achieved using multi-sparse constraint representation (MSCR), and the Alternating Direction Method of Multipliers (ADMM) is used for calculation. Extensive experiments demonstrated the proposed algorithm’s effectiveness and compared it with state-of-the-art algorithms in subjective judgments and objective indicators. The experimental results fully demonstrate the proposed algorithm’s superiority and efficacy.

In the volatile, uncertain, complex, and ambiguous environment (VUCA), employees can better match the organization and jobs by crafting their job perceptions, work tasks, and relationships, which is valuable to maintain organizational sustainable competitiveness and promote employees’ personal growth. This study explores the influence mechanisms of job autonomy and work meaning on employees’ job-crafting behaviors and the moderating effect of perceived organizational change through a survey of 318 employees in Chinese companies. The results show that job autonomy and work meaning can promote employees’ job-crafting behaviors by increasing individuals’ harmonious work passion. The indirect effects of job autonomy and work meaning on employee job-crafting behaviors through harmonious work passion are stronger for individuals with high perceived organizational change relative to those with low perceived organizational change. Organizations should concentrate on job redesign to improve employees’ job autonomy and work meaning. A climate of change should also be created within the organization to keep employees aware of the crisis. Meanwhile, employees should actively use work resources to meet the changing needs of organizational development and promote individual career development through job-crafting behaviors.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296–7.979, P =.012), a platelet count ≤ 15,000/μL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044–2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088–3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360–5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717–15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532–12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Multiple myeloma (MM), a hematologic malignancy, is characterized by malignant plasma cells clonal proliferation. Many evidences indicated the indirect interaction between hypoxic environment and immune state in MM tumorigenesis, but the underlying mechanism remains unclear. MM-related datasets were downloaded from the Gene Expression Omnibus (GEO) database. The R packages were applied for screening protective differentially expressed genes (DEGs) and risk DEGs. The signature was constructed based the most prognostic gene signature in the training and assessed in the validation cohorts. The immune cell infiltration, the expression of the HLA family and immune checkpoint genes inside the low- and high-risk groups were compared to determine the differences in immune infiltration and immunotherapy responses. Moreover, the expression of HLA families and immune checkpoints inside the low- and high-risk groups was markedly disordered. The results indicated hypoxia- and immune-related genes, including CHRDL1, DDIT4, DNTT, FAM133A, MYB, PRR15, QTRT1, and ZNF275, were identified and used to construct a prognostic signature. Role of DDIT4 in multiple myeloma was confirmed in vivo and in vitro. DDIT4 knockdown inhibited MM cell viability, migration and invasion potential as well as promoted myeloma cells apoptosis under hypoxia. Taken together, our study may contribute to the treatment and prognosis prediction of MM.

Abstract Multiple myeloma (MM) is the second‐ranking malignancy in hematological tumors. The pathogenesis of MM is complex with high heterogeneity, and the development of the disease is a multistep process. Chromosomal translocations, aneuploidy, genetic mutations, and epigenetic aberrations are essential in disease initiation and progression. The correlation between MM cells and the bone marrow microenvironment is associated with the survival, progression, migration, and drug resistance of MM cells. In recent decades, there has been a significant change in the paradigm for the management of MM. With the development of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, chimeric antigen receptor T‐cell therapies, and novel agents, the survival of MM patients has been significantly improved. In addition, nanotechnology acts as both a nanocarrier and a treatment tool for MM. The properties and responsive conditions of nanomedicine can be tailored to reach different goals. Nanomedicine with a precise targeting property has offered great potential for drug delivery and assisted in tumor immunotherapy. In this review, we summarize the pathogenesis and current treatment options of MM, then overview recent advances in nanomedicine‐based systems, aiming to provide more insights into the treatment of MM.