Severe inflammation in C57/BL6 mice leads to prolonged cognitive impairment by initiating the IL-1ß/TRPM2 pathway.

BACKGROUND: Sepsis could lead to chronic cognitive impairment by unclear molecular mechanisms. Transient receptor potential melastatin-2 (TRPM2) is essential against immunity-related activities and inflammation. Our study attempted to decipher the relationship between cognitive impairment caused by severe inflammation and TRPM2 expression levels. METHODS: Severe inflammation was induced by intraperitoneally injecting C57/BL6 mice with a high dosage (5 mg kg-1) of Lipopolysaccharide (LPS). Fear conditioning and a Morris water maze test were performed to examine the cognitive abilities of the mice. Moreover, the signaling and expression of pro-inflammatory cytokines and TRPM2 were measured using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry and immunofluorescence staining helped to determine the astrocyte apoptosis rate. RESULTS: Severe inflammation can lead to long-term cognitive impairment in C57/BL6 mice. The interleukin-1 beta (IL-1ß) levels intra-hippocampus were significantly elevated until P14 post-LPS introduction. At both P7 and P14, there is an up-regulation of TRPM2 expression within hippocampus. Administration of recombinant IL-1ß to astrocytes results in a significant up-regulation of TRPM2 expression. IL-1ß or TRPM2 level knockdown helped counter the cognitive impairment caused by significant inflammation. CONCLUSIONS: A continuous increase in IL-1ß levels within the hippocampus can lead to cognitive impairment by enhancing TRPM2 levels caused by severe inflammation.

A retrospective study of autologous hematopoietic stem cell transplantation for peripheral T-cell lymphoma: pre-transplant patients with partial remission benefit from post-transplant maintenance therapy.

Background: Whether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear. In this study, we aimed to analyze the efficacy of ASCT and post-transplant maintenance therapy in PTCL. Methods: We retrospectively analyzed the clinical data of 69 patients with PTCL who underwent ASCT at our center between November 2001 and November 2021. According to the patients' intention, thirty patients received post-transplant maintenance treatment, whereas 39 did not. The overall survival (OS) and progression-free survival (PFS) between the groups were compared using the log-rank test. Results: At a median follow-up of 36 months, the entire cohort's 3-year OS and PFS were 67.8% and 53.0%, respectively. The 3-year OS and PFS of patients with CR1, CR2, and PR were 85.3% and 65.4%, 80.0% and 60.0%, and 38.4% and 32.0%, respectively (OS: P=0.001; PFS: P=0.003). The relapse rates between the groups with or without maintenance therapy were 26.7% vs. 52.2%, the 3-year OS was 86.0% vs. 54.2% (P=0.004), and the 3-year PFS was 73.3% vs. 37.5% (P=0.004). Further analysis revealed that the efficacy of maintenance therapy was not significant in patients with CR1 and CR2, whereas patients with PR benefited from maintenance therapy. The relapse rate of patients with PR who received or did not receive maintenance therapy was 33.3% vs. 78.7%, 3-year OS was 66.7% vs. 21.9% (P=0.007), and 3-year PFS was 66.7% vs. 12.5% (P=0.004). Conclusions: Patients with CR in PTCL benefit from ASCT, and post-transplant maintenance therapy reduces the relapse rate and significantly improves OS and PFS in patients with PR.

Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review.

BACKGROUND: More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS: HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS: Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION: Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.

Treatment of extranodal NK/T-cell lymphoma: From past to future.

Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.

A retrospective cohort study of polatuzumab vedotin combined with immunochemotherapy in Chinese patients with relapse/refractory diffuse large B cell lymphoma.

Background: There are no standard therapies for patients with relapse/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are ineligible for transplantation. Recently, polatuzumab vedotin (pola) combined with rituximab and bendamustine (pola-BR) has been validated in clinical trials. However, pola is not approved in China and clinical data in Chinese population is still lacking. This study is intended to preliminarily evaluate the clinical effectiveness of this regimen in China. Methods: This study retrospectively evaluated the efficacy and tolerability of pola-BR regimen in Chinese R/R DLBCL patients treated in a compassionate use program (CUP; pola CUP) after failing ≥2 prior regimens. Patients participated in CUP at 4 Chinese centers from December 2019 to July 2020 were enrolled. The outcomes were the overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS). Adverse events (AEs) were collected. Results: A total of 28 patients enrolled in the pola CUP were included. At data analysis cut-off (30 September 2020), the best overall response (BOR) rate was 71.4%, and a CR rate of 25.0% was obtained. The estimated median PFS of all patients was 200 [95% confidence interval (CI): 97 to not evaluable (NE)] days. The most common AEs were thrombocytopenia (32.1%), neutropenia (28.6%), and fever (14.3%). High-grade (grade ≥2) peripheral neuropathy (PN) was not observed. Conclusions: These preliminary data suggested that the pola-BR regimen has promising efficacy and tolerable safety in Chinese transplantation ineligible R/R DLBCL patients. Hence, pola-BR may be an optional regimen. Considering the limited sample size and short follow-up, larger sample and long-term survival outcome studies are warranted.

Plasma EBV-DNA and peripheral blood mononuclear cell EBV-DNA have disparate clinical relevance in patients with extranodal NK/T-cell lymphoma.

BACKGROUND: Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related hematological malignancy. The presence of EBV-DNA in peripheral blood is a widely used ENKTCL tumor marker. However, there is no consensus on the preferred blood specimen type for EBV testing. Furthermore, discordance between EBV-based and imaging-based disease assessments is common, and how to interpret this discordance is important. METHOD: We retrospectively analyzed the data of ENKTCL patients in the Affiliated Cancer Hospital of Zhengzhou university and Sun Yat-sen University Cancer Center. All EBV-DNA and imaging-based disease assessment data were collected at diagnosis, during treatment, at the end of treatment, and during follow-up. We compared matched plasma EBV-DNA and peripheral blood mononuclear cell (PBMC) EBV-DNA and matched EBV-based and imaging-based assessments to uncover their clinical relevance. RESULT: A total of 450 patients with adequate data were included, of whom 278 had plasma EBV-DNA data, 250 had PBMC EBV-DNA data, and 78 had matched plasma and PBMC EBV-DNA data. No significant correlations were found between PBMC and plasma EBV-DNA and between PBMC EBV-DNA and imaging-based assessment, but patients with positive PBMC EBV-DNA at diagnosis or intermittently/persistently positive PBMC EBV-DNA during follow-up had poorer survival. In contrast, plasma EBV-DNA strongly correlated with lymphoma status. Detectable pre- and post-treatment plasma EBV-DNA was associated with significantly worse survival. Patients with early-stage disease who had detectable plasma EBV-DNA at the end of treatment shared similar survival to those with advanced-stage disease, even if their imaging-based assessments were negative. For disease relapse monitoring, 78 (55.7%) episodes of relapse were detected by both imaging and plasma EBV-DNA; 58 (41.4%) detected by plasma EBV-DNA earlier than imaging, with a median time of 9.3 (0.3 - 37.8) months; and only 4 (2.9%) detected by plasma EBV-DNA later than imaging. The sensitivities of plasma EBV-DNA, PET/CT, and CT/MRI were 97.1%, 76.8%, and 45.1%, respectively, and their specificities were 91.7%, 84.2%, and 96.7%, respectively. Analysis of EBV kinetic patterns in EBV+/imaging- episodes revealed that relapse occurred only in patients with intermittently/persistently positive plasma EBV-DNA. Persistent plasma EBV+ was also seen in patients after autologous hematopoietic stem cell transplantation. Occasional EBV+ was not associated with relapse. CONCLUSION: Plasma and PBMC EBV-DNA have different clinical relevance in ENKTCL patients. PBMC EBV-DNA does not correlate with imaging-based disease assessment. PBMC or even whole blood should not be used for response evaluation and relapse monitoring. However, PBMC EBV-DNA still has prognostic value. Plasma EBV-DNA is strongly related to tumor status and is not only a prognosticator at diagnosis and end of treatment, but also a sensitive marker in relapse monitoring compared to PET/CT and CT/MRI. The specificity of plasma EBV-DNA is relatively low, but when EBV-DNA kinetic patterns are considered, it can identify at-risk patients.

MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma.

Anthracycline-based chemotherapy resistance represents a major challenge in diffuse large B-cell lymphoma (DLBCL). MiRNA and gene expression profiles (n = 47) were determined to uncover potential chemoresistance mechanisms and therapeutic approaches. An independent correlation between high expression of miRNA-363-3p and chemoresistance was observed and validated in a larger cohort (n = 106). MiRNA-363-3p was shown to reduce doxorubicin-induced apoptosis and tumor shrinkage in in vitro and in vivo experiments by ectopic expression and CRISPR/Cas9-mediated knockout in DLBCL cell lines. DNA methylation was found to participate in transcriptional regulation of miRNA-363-3p. Further investigation revealed that dual specificity phosphatase 10 (DUSP10) is a target of miRNA-363-3p and its suppression promotes the phosphorylation of c-Jun N-terminal kinase (JNK). The miRNA-363-3p/DUSP10/JNK axis was predominantly associated with negative regulation of homologous recombination (HR) and DNA repair pathways. Ectopic expression of miRNA-363-3p more effectively repaired doxorubicin-induced double-strand break (DSB) while enhancing non-homologous end joining repair and reducing HR repair. Targeting JNK and poly (ADP-ribose) polymerase 1 significantly inhibited doxorubicin-induced DSB repair, increased doxorubicin-induced cell apoptosis and tumor shrinkage, and improved the survival of tumor-bearing mice. In conclusion, the miRNA-363-3p/DUSP10/JNK axis is a novel chemoresistance mechanism in DLBCL that may be reversed by targeted therapy.

Treatment of upper eyelid third-degree burns by dispersed implantation of very small autologous columnar skin grafts: A pilot study of a new method.

OBJECTIVE: This retrospective study compared the effectiveness of dispersed implantation of very small autologous columnar skin (SCS) grafts and full-thickness skin grafts (FTSGs) for treating upper eyelid third-degree burns. METHODS: Fourteen patients and 26 eyes with granulation tissue formed by third-degree upper eyelid burns were enrolled in the study from August 2017 to June 2020. The experimental group of 6 patients with 11 eyes was treated with SCS grafts. The control group of 8 patients with 15 eyes was treated with FTSGs. The survival rate of the grafts, healing time, SCS diameter, upper eyelid movement distance (ULMD), visual analogue scale (VAS) score for patient satisfaction, and Vancouver Scar Scale (VSS) score were evaluated. RESULTS: The difference in the survival rate between the two groups was not statistically significant (P = 0.06). The ULMD and VAS scores in the experimental group were higher than those in the control group (P < 0.05). The healing time was longer in the experimental group than in the control group (P < 0.05). The VSS scores of the donor site and the skin grafting site in the experimental group were lower than those in the control group (P < 0.05). CONCLUSION: Unlike classical skin grafts, SCS implantation surgery can restore the appearance of the upper eyelid, and there is no obvious scar at the donor site. This can be a viable alternative to traditional FTSGs with potential benefits.

Influence mechanism of structure on shear mechanical deformation characteristics of loess-steel interface.

The mechanical properties of loess-steel interface are of great significance for understanding the residual strength and deformation of loess. However, the undisturbed loess has significant structural properties, while the remolded loess has weak structural properties. There are few reports on the mechanical properties of loess-steel interface from the structural point of view. This paper focused on the ring shear test between undisturbed loess as well as its remolded loess and steel interface under the same physical mechanics and test conditions (water content, shear rate and vertical pressure), and explored the influence mechanism of structure on the mechanical deformation characteristics of steel-loess interface. The results show that the shear rate has little effect on the residual strength of the undisturbed and remolded loess-steel interface. However, the water content has a significant influence on the residual strength of the loess-steel interface, moreover, the residual internal friction angle is the dominant factor supporting the residual strength of the loess-steel interface. In general, the residual strength of the undisturbed loess-steel interface is greater than that of the remolded loess specimen (for example, the maximum percentage of residual strength difference between undisturbed and remolded loess specimens under the same moisture content is 6.8%), which is because that compared with the mosaic arrangement structure of the remolded loess, the overhead arrangement structure of the undisturbed loess skeleton particles makes the loess particles on the loess-steel interface re-adjust the arrangement direction earlier and reach a stable speed relatively faster. The loess particles with angular angles in the undisturbed loess make the residual internal friction between the particles greater than the smoother particles of the remolded loess (for example, the maximum percentage of residual cohesion difference between undisturbed and remolded loess specimens under the same vertical pressure is 4.29%), and the intact cement between undisturbed loess particles brings stronger cohesion than the remolded loess particles with destroyed cement (for example, the maximum difference percentage of residual cohesion between undisturbed and remolded soil specimens under the same vertical pressure is 33.80%). The test results provide experimental basis for further revealing the influence mechanism of structure, and parameter basis for similar engineering construction.

Multiple rechallenges with anti-PD-1 immunotherapy in patients with checkpoint inhibitor-related pneumonitis: A report of two cases.

INTRODUCTION: With the expanding use of immune checkpoint inhibitors (ICIs) in patients with various types of cancers, many more patients are experiencing checkpoint inhibitor-related pneumonitis (CIP). After recovery from CIP, some patients are rechallenged with ICI therapy. The CIP will recur in a considerable proportion of rechallenged patients. When severe or recurrent CIP (rCIP) occurs, ICI therapy is usually terminated, resulting to treatment failure and tumour progression. The feasibility of multiple rechallenges with immunotherapy in patients with rCIP is unknow. CASE PRESENTATION: Two patients with refractory classical Hodgkin lymphoma (cHL) were treated with anti-programmed cell death protein 1 (PD-1) immunotherapy. The lymphoma responded well to the ICI therapy, but both patients experienced CIP. The immunotherapy was suspended and steroid was introduced to treated the CIP. When the CIP resolved, however, the lymphoma progressed. MANAGEMENT AND OUTCOME: The patients were rechallenged with anti-PD-1 immunotherapy in the absence of alternative treatment options. The lymphoma responded again, but the CIP recurred. The immunotherapy was suspended again and steroid was reintroduced. These episodes repeated multiple times. At the time of submission of this manuscript, the tumour in both patients has been controlled for more than 4 years, and the immunotherapy is still continuing. CONCLUSION: Multiple rechallenges with immunotherapy is feasible in selected patients with rCIP.

Microstructure of unsaturated loess and its influence on strength characteristics.

Previous studies have shown that structure has a significant influence on the mechanical deformation of unsaturated loess, but there is little published information focused on the influence mechanism of microstructure and mesostructure on the mechanical properties of loess. In this paper, the unsaturated undisturbed loess and its remolded loess under the same physical condition were taken as the research objects. The unsaturated triaxial shear tests with constant suction and net confining pressure were carried out, and the microstructure differences between the two are compared by using SEM and CT scanning to reveal the influence of structure on strength characteristics. The test results show that the cohesion and internal friction angle of undisturbed loess are greater than those of remolded loess. The angle of undisturbed soil particles is obvious, and the particles are bracket contact with good cementation. The remolded loess particles are close to round shape, and the particles are inlaid contact with destroyed cementation. The average radius of undisturbed soil is higher than that of remolded soil, indicating that there are bracket pores in undisturbed soil, but the bracket structure and macropores are deformed during shear deformation, and good structural and cementation ensure the strength of loess specimens.

Anti-Angiogenic Agent Combined with Anti-PD-1 Immunotherapy Showed Activity in Patients With Classical Hodgkin Lymphoma Who Have Failed Immunotherapy: A Retrospective Case Report Study.

Background: PD-1/PD-L1 inhibitor immunotherapy has showed impressive activity in various cancers, especially relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). However, acquired resistance is inevitable for most patients. Sometimes severe side effects also lead to treatment termination. When immunotherapy failed, alternative treatment options are limited. In the past few years, we have used the anti-angiogenic agent apatinib and PD-1 inhibitor camrelizumab to treat cHL patients who failed prior immunotherapy. In this study, we analyzed the data of these patients. Patients and Methods: Patients with r/r cHL who had failed immunotherapy and subsequently received apatinib-camrelizumab (AC) combination therapy were included in this study. Patient data were collected from medical records and follow-up system. The efficacy and safety of AC therapy were analyzed. Results: Seven patients who failed immunotherapy were identified in our database, of which five patients acquired immunotherapy resistance and two patients experienced severe side effects. They received a combination of camrelizumab (200 mg every four weeks) and apatinib (425 mg or 250 mg per day). As of the cut-off date, these patients had received a median of 4 cycles (range, 2 - 31) of treatment. Two (2/7) patients achieved complete response, four (4/7) partial response, and one (1/7) stable disease. The median progression-free survival was 10.0 months (range, 2.0 - 27.8). Low-dose apatinib (250 mg) plus camrelizumab was well tolerated and had no unexpected side effects. Besides, no reactive cutaneous capillary endothelial proliferation was observed in AC-treated patients. Conclusions: Low dose apatinib plus camrelizumab might be a promising treatment option for r/r cHL patients who have failed immunotherapy. This combination treatment is worthy of further investigation in more patients including solid cancer patients who have failed immunotherapy.

Primary Testicular Lymphoma with Central Nervous System Relapse Was Successfully Treated by a Chemo-Free Regimen: A Case Report and Literature Review.

Primary testicular lymphoma (PTL) is a rare malignancy of testis. Although the multimodality treatment (including orchiectomy, systemic chemotherapy, scrotal radiotherapy, and preventive central nervous system (CNS)-targeted treatment) is widely used to treat PTL, recurrence, especially CNS recurrence, occurred frequently. Patients with relapsed PTL have a dismal prognosis and limited treatment options. In this report, we described the case of a 63-year-old man with early-stage PTL. The patient received the multimodality treatment, but CNS relapse occurred 3 months following the front-line therapy. We gave him a combined chemo-free regimen treatment, including rituximab, ibrutinib, and lenalidomide (RIL), based on the tumor's gene mutation profile and the patient's preference. A complete response was achieved after the first cycle of treatment. Whole-brain radiotherapy was delivered as consolidative treatment following three more cycles of RIL. Thereafter, ibrutinib and lenalidomide continued as maintenance treatment. As of the submission of this manuscript, the response has lasted for more than 16 months. Based on the case, we believe chemo-free regimen RIL might be a favorable approach for PTL patients with CNS relapse, especially those frail elderly patients, when alternative treatments are not available.

Durable Response to Sintilimab and Chidamide in a Patient With Pegaspargase- and Immunotherapy-Resistant NK/T-Cell Lymphoma: Case Report and Literature Review.

The prognosis of patients with relapsed/refractory NK/T-cell lymphoma (NKTCL) is dismal. Immunotherapy has showed encouraging anti-tumor activity in patients with asparaginase-resistant NKTCL; however, only a portion of patients benefit and the median response duration is rather short. Treatment strategies have not been identified for immunotherapy-resistant NKTCL. We describe a patient with primary cutaneous NKTCL experienced disease progression after pegaspargase-based chemotherapy and PD-1 inhibitor (sintilimab)-based immunotherapy. Following a combined treatment of sintilimab and the HDAC inhibitor chidamide, the patient achieved a durable complete molecular response with mild toxicity. This case indicates that the combination of PD-1 inhibitor and HDAC inhibitor might be a treatment choice for immunotherapy-resistant NKTCL.

A genetic predictive model for precision treatment of diffuse large B-cell lymphoma with early progression.

BACKGROUND: Early progression after the first-line R-CHOP treatment leads to a very dismal outcome and necessitates alternative treatment for patients with diffuse large B-cell lymphoma (DLBCL). This study aimed to develop a genetic predictive model for early progression and evaluate its potential in advancing alternative treatment. METHODS: Thirty-two hotspot driver genes were examined in 145 DLBCL patients and 5 DLBCL cell lines using next-generation sequencing. The association of clinical features, cell-of-origin, double expression, positive p53 protein, and gene alterations with early progression was analyzed, and the genetic predictive model was developed based on the related independent variables and assessed by the area under receiver operating characteristic. The potential of novel treatment based on the modeling was investigated in in-vitro DLBCL cell lines and in vivo xenograft mouse models. RESULTS: The frequency of CD79B (42.86% vs 9.38%, p = 0.000) and PIM1 mutations (38.78% vs 17.71%, p = 0.005) showed a significant increase in patients with early progression. CD79B and PIM1 mutations were associated with complex genetic events, double expression, non-GCB subtype, advance stage and unfavorable prognosis. A powerful genetic predictive model (AUROC = 0.771, 95% CI: 0.689-0.853) incorporating lactate dehydrogenase levels (OR = 2.990, p = 0.018), CD79B mutations (OR = 5.970, p = 0.001), and PIM1 mutations (OR = 3.021, p = 0.026) was created and verified in the other cohort. This modeling for early progression outperformed the prediction accuracy of conventional International Prognostic Index, and new molecular subtypes of MCD and Cluster 5. CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling. Since the two inhibitors failed to decrease BCL2 level, BCL2 inhibitor (venetoclax) was added and demonstrated to enhance their apoptosis-inducing activity in mutant cells with double expression. CONCLUSIONS: The genetic predictive model provides a robust tool to identify early progression and determine precision treatment. These findings warrant the development of optimal alternative treatment in clinical trials.

Combining PD-1 Inhibitor Nivolumab with Radiotherapy Successfully Treated a Patient with Refractory Primary Mediastinal Large B-Cell Lymphoma: A Case Report and Literature Review.

Primary mediastinal large B-cell lymphoma (PMBCL) is relatively infrequent and generally has a good prognosis with standard immunochemotherapy. However, treatment options are limited for patients with relapsed/refractory PMBCL who are ineligible for stem cell transplantation. In this report, we treated a refractory PMBCL patient, who did not respond to salvage chemotherapy, with combined nivolumab and radiotherapy. The patient achieved a complete remission with mild adverse reactions and has survived without relapse 2 years after treatment.

Camrelizumab plus apatinib successfully treated a patient with advanced esophageal squamous cell carcinoma.

Aim: Advanced esophageal squamous cell carcinoma (ESCC) is a lethal disease with poor response to conventional chemotherapy. Immunotherapy showed better activity than chemotherapy in late-line treatment. However, the rate and duration of response are far from satisfactory. The efficacy of an anti-angiogenic agent combined with immunotherapy for ESCC is unknown. Results: A patient with ESCC experienced disease relapse after chemo-radiotherapy. The disease progressed after combined chemotherapy. A combination regimen of the PD-1 inhibitor camrelizumab and the anti-angiogenic agent apatinib was administered. The patient achieved a PET/CT-confirmed durable complete response with mild toxicity. Conclusion: The PD-1 inhibitor combined with the anti-angiogenic agent is effective and safe for the treatment of ESCC. This regimen is worth investigation in clinical trials.

A Trial of the Safety and Efficacy of Chemotherapy Plus Anlotinib vs Chemotherapy Alone as Second- or Third-Line Salvage Treatment for Advanced Non-Small Cell Lung Cancer.

PURPOSE: Anlotinib is a newly developed oral multitarget tyrosine kinase inhibitor. We retrospectively evaluated the toxicity and clinical efficacy of chemotherapy combined with anlotinib versus chemotherapy alone for metastatic/advanced non-small cell lung cancer (NSCLC) in patients who failed first- or second-line systemic treatment in China. PATIENTS AND METHODS: In this retrospective trial, ninety-four advanced NSCLC patients received chemotherapy combined with anlotinib (n = 41) or chemotherapy alone (n = 53) in Henan Cancer Hospital. We recorded the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse events (AEs). RESULTS: In the anlotinib plus chemotherapy group, eleven patients (27%) achieved a PR (partial response), and twenty-one patients (51%) achieved SD (stable disease), with an ORR of 27% and a DCR of 78%. In the chemotherapy alone group, eight patients (15%) achieved a PR, and nineteen patients (36%) had SD, with an ORR of 15% and a DCR of 51%. The ORR in the combination arm was slightly, but not obviously, higher than that in the chemotherapy arm (27% vs 15%, p > 0.05). In addition, the DCR was significantly higher in the combination arm than in the chemotherapy alone arm (78% vs 51%, p=0.007). At the end of follow-up, patients in the combination arm had a 1.5-month longer median PFS than patients in the chemotherapy arm; this difference was statistically significant (5.0 vs 3.5, p=0.002). The median OS was not achieved at the final analysis. The hematological and nonhematological toxicities were well tolerated and controlled. In general, most toxicity was limited to grade I or II, well tolerated and controlled. CONCLUSION: Our study suggests that anlotinib combined with chemotherapy may be an effective and well-tolerated treatment for advanced NSCLC in patients who fail first- or second-line therapy.

Estimation of soil salt content by combining UAV-borne multispectral sensor and machine learning algorithms.

Soil salinization is a global problem closely related to the sustainable development of social economy. Compared with frequently-used satellite-borne sensors, unmanned aerial vehicles (UAVs) equipped with multispectral sensors provide an opportunity to monitor soil salinization with on-demand high spatial and temporal resolution. This study aims to quantitatively estimate soil salt content (SSC) using UAV-borne multispectral imagery, and explore the deep mining of multispectral data. For this purpose, a total of 60 soil samples (0-20 cm) were collected from Shahaoqu Irrigation Area in Inner Mongolia, China. Meanwhile, from the UAV sensor we obtained the multispectral data, based on which 22 spectral covariates (6 spectral bands and 16 spectral indices) were constructed. The sensitive spectral covariates were selected by means of gray relational analysis (GRA), successive projections algorithm (SPA) and variable importance in projection (VIP), and from these selected covariates estimation models were built using back propagation neural network (BPNN) regression, support vector regression (SVR) and random forest (RF) regression, respectively. The performance of the models was assessed by coefficient of determination (R 2), root mean squared error (RMSE) and ratio of performance to deviation (RPD). The results showed that the estimation accuracy of the models had been improved markedly using three variable selection methods, and VIP outperformed GRA and GRA outperformed SPA. However, the model accuracy with the three machine learning algorithms turned out to be significantly different: RF > SVR > BPNN. All the 12 SSC estimation models could be used to quantitatively estimate SSC (RPD > 1.4) while the VIP-RF model achieved the highest accuracy (R c 2 = 0.835, R P 2 = 0.812, RPD = 2.299). The result of this study proved that UAV-borne multispectral sensor is a feasible instrument for SSC estimation, and provided a reference for further similar research.

High-Grade B-Cell Lymphomas, Not Otherwise Specified: A Study of 41 Cases.

PURPOSE: To analyze the clinical and pathological characteristics, treatment, and prognosis of high-grade B-cell lymphomas, not otherwise specified (HGBL, NOS), and to increase awareness of this type of lymphoma. PATIENTS AND METHODS: We collected clinical and pathological data of 41 cases of newly diagnosed HGBL, NOS, and analyzed diagnosis, prognosis and treatment to examine progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 41 cases studied, the median PFS was 6.0 months and the median OS was 18.0 months. Compared with patients treated with the R-CHOP regimen, patients treated with a high-intensity chemotherapy (DA-EPOCH-R, R-CODOX-M/IVAC, or R-Hyper-CVAD) had superior PFS and OS (PFS: χ2=4.173, P=0.041; OS: χ2=5.200, P=0.023). A subgroup analysis showed that the OS for the double-expressor lymphoma (DEL) was inferior to that for the non-DEL (χ2=4.563, P=0.033), and this trend was also seen for the single-hit lymphoma with MYC rearrangement (SHL) and the non-SHL (χ2=4.955, P=0.026). Patients with low International Prognostic Index (IPI) scores (≤2) had better survival rates than those with high scores (>2) (PFS: χ2=6.482, P=0.011; OS: χ2=10.156, P=0.001). CONCLUSION: HGBL, NOS is associated with a high degree of malignancy, short survival period, and substantial extranodal involvement. High-intensity chemotherapy may improve patient prognosis. While IPI scores statistically correlated with the prognosis, SHL and DEL correlated with an inferior survival rate. New and improved treatments will be needed for HGBL, NOS.