Rapid response in relapsed follicular lymphoma to novel anti-CD19 CAR-T therapy with pseudo-progression and cytomegalovirus infection: A case report.

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV. After tumor burden was reduced with Obinutuzumab and Duvelisib, the patient was infused novel CD19 CAR-T cells at a dose of 3 × 106 cells/ kg. Then he experienced a rapid response and achieved almost complete remission by day 26. Only grade 2 CRS, bilateral submaxillary lymph node enlargement and cytomegalovirus (CMV) infection occurred without neurotoxicity, and the patient's condition improved after a series of symptomatic treatments. In addition, CAR copy number peaked at 532,350 copies/µg on day 15 and continued to expand for 5 months. This may be the first case report of RV preparation of novel CD19 CAR-T cells for direct treatment of recurrent follicular lymphoma. We will observe its long-term efficacy and conduct trials in more patients in the future.

Evaluation of multi-parameter MRI in preoperative staging of endometrial carcinoma.

Background: Endometrial carcinoma (EC) is a prevalent gynecological malignancy, necessitating accurate preoperative staging for effective treatment planning. This study explores the application value of multi-parameter MRI in diagnosing and staging endometrial cancer. Methods: Seventy-six patients diagnosed with endometrial cancer underwent 3.0 T pelvic MRI within two weeks before surgery. Imaging data were analyzed based on FIGO clinical staging criteria. The study assessed the sensitivity, specificity, positive predictive value, and negative predictive value of MRI for each stage. Results: Postoperative pathology confirmed 71 cases of endometrial adenocarcinoma, 3 serous adenocarcinoma, and 2 clear cell carcinomas. MRI staging showed a high consistency (Kappa value = 0.786) with postoperative pathology. The overall accuracy of MRI diagnosis was 86.8%. Sensitivity and specificity varied for each stage: IA (91.3%, 96.2%), IB (88.6%, 93.8%), II (97.4%, 89.2%), and III (84.2%, 100%). Conclusion: While there was a slight misdiagnosis rate, the overall accuracy of preoperative MRI for endometrial cancer was high, aiding in precise diagnosis and clinical staging. MRI effectively identified myometrial infiltration, cervical involvement, paracentral extension, and lymph node metastasis. Further research with larger sample sizes is recommended for enhanced reliability.

Comparative Safety Assessment of High and Low Doses of Anlotinib in Combination with PD-1 Monoclonal Antibody for Advanced Non-small Cell Lung Cancer Patients.

Background: The advent of immunotherapy has revolutionized non-small cell lung cancer (NSCLC) treatment. Anlotinib (AN), a multitargeted tyrosine kinase inhibitor, holds promise in combination with PD-1 monoclonal antibody therapy. Understanding the impact of optimal dosage is pivotal. Objective: This study aims to assess the comparative efficacy of high-dose AN versus low-dose AN when combined with PD-1 monoclonal antibody for the treatment of NSCLC. Methods: A total of 70 patients with NSCLC undergoing PD-1 monoclonal antibody therapy at our hospital from June 2020 to January 2022 were selected. The low-dose group (n=33) received AN at 8 mg and 10 mg. In comparison, the high-dose group (n=37) received AN at 12 mg. Comparative analyses included assessment of clinical efficacy, adverse reactions, prognosis, survival, changes in T lymphocyte subsets, inflammatory factors pre and post-chemotherapy, and treatment satisfaction. Results: No significant difference was observed in clinical efficacy and prognosis between the two groups (P > .05). The low-dose group exhibited fewer adverse reactions and inflammatory responses, along with improved immune function post-treatment (P < .05). Treatment satisfaction was higher in the low-dose group compared to the high-dose group (P < .05). Conclusions: Findings suggest that combining low-dose AN with PD-1 monoclonal antibody therapy is a safer approach in the treatment of advanced NSCLC. These findings advocate for the adoption of a tailored, lower-dose AN regimen, presenting a clinically sound and patient-centered strategy in the ongoing pursuit of optimized treatment modalities for advanced NSCLC.

Predictive response and outcome of peripheral CD4+ T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients.

BACKGROUND: The identification of predictive biomarkers for patient stratification in immunotherapy is of utmost importance, given the limited benefit observed in certain populations. However, only limited information is so far available on the association between peripheral CD4+ T cell subpopulations and immunotherapy for advanced gastric cancer. Our current report aimed to investigate the predictive value of peripheral CD4+ T cell subpopulations in advanced gastric cancer patients treated with immunotherapy. METHODS: A retrospective cohort analysis of 169 advanced gastric cancer patients treated with sintilimab combined with capecitabine and oxaliplatin in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between June 2019 and October 2022 was conducted. Clinical outcomes of peripheral CD4+ T cell subpopulations were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier method and the univariate and multivariate Cox proportional hazards regression models. RESULTS: The optimal cutoff values for percentages of CD4+ T cells, naive CD4+ T cells (CD4+ Tn), memory CD4+ T cells (CD4+ Tm), central memory CD4+ T cells (CD4+ Tcm) and effector memory CD4+ T cells (CD4+ Tem) expressing PD-1 were 30.16 %, 17.79 %, 42.49 %, 31.54 % and 74.64 %, respectively. It was found that the percentages of CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). This correlation was also observed in the PD-L1 combined positive score (CPS) ≥ 5 populations. Univariate and multivariate Cox regression analyses indicated that lower CD4+ T, CD4+ Tn, CD4+ Tm, CD4+ Tcm and CD4+ Tem expressing PD-1 were independent risk factors of PFS and OS in advanced gastric cancer patients treated with combined immunotherapy and chemotherapy. CONCLUSION: The peripheral CD4+ T cell subpopulations demonstrated the high predictive value for therapeutic response and prolonged survival outcomes in advanced gastric cancer patients. CD4+ T cell subpopulations have the potential in predicting and screening benefit populations in advanced gastric cancer patients.

Chinese expert consensus on the management of patients with hematologic malignancies infected with SARS-CoV-2.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

Exploring college students' continuance learning intention in data analysis technology courses: the moderating role of self-efficacy.

Introduction: In today's digital economy, data resources have gained strategic recognition. Enterprises view data analytic capabilities as a core organizational competitiveness. This study explored factors influencing college students' continuance learning intention in data analysis technology courses to inform the role of self-efficacy on the relationship between interactivity and continuance learning intention. Methods: The research model underpinning the study was based on the Stimulus-Organism-Response model and flow theory. The model was validated using SmartPLS. A total of 314 valid questionnaires were collected via the standard online survey approach. Results: Among internal factors, study results showed both cognitive interest and self-efficacy had significant positive effects on continuance learning intention. Also, cognitive interest had a significant positive effect on self-efficacy. Among external stimuli, content quality, software quality, and interactivity had significant positive effects on self-efficacy. Software quality did not have a significant effect on cognitive interest. Importantly, self-efficacy registered a significant moderating role on the relationship between interactivity and continuance learning intention.

Clinicopathological characteristics of HER2-low breast cancer: a retrospective study.

Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P < 0.001). Significant differences between HER2-low BCs and Her2-0 BCs were observed in lymph node ratio (LNR) (mean rank, 215 vs. 188 P = 0.014), estrogen receptor (ER)expression (90.5% vs. 62.4% P < 0.001), progesterone receptor (PR) expression (84.3% vs. 56.9% P < 0.001), Ki-67 expression (46.4% vs. 61.5% P < 0.001), androgen receptor (AR) expression (68% vs. 50.5% P < 0.001), adjuvant chemotherapy (69% vs. 79.8% P = 0.03). HER2-low BCs had lower histological grade than HER2-0 BCs, with grade I-II (68.7% vs. 43.1%) and grade III (22.2% vs. 43.1%) P < 0.01. No statistical differences were detected between the two groups for DFS and DDFS. Our results demonstrated that HR and AR status was closely related to HER2-low breast cancers. Further exploration about survival prognosis of HER2-low breast cancer is badly needed.

A rare presentation of Sintilimab-induced swelling along the vessels: Case report.

RATIONALE: Immune-related adverse events are occasionally reported in Sintilimab treatment. This study reports a forward and reverse swelling case along the vein after infusion of Sintilimab. At present, swelling along the vascular direction during peripheral infusion are limitedly reported at home and abroad, especially when choosing a vein with thick, elastic, and good blood return. PATIENT CONCERNS: A 56-year-old male who suffered from esophageal cancer and liver cancer and received albumin-bound paclitaxel and nedaplatin chemotherapy in combination with Sintilimab immunotherapy appeared swelling along the vessel after infusion of Sintilimab. The patient was punctured 3 times. DIAGNOSES: Sintilimab-induced vascular edema may be a side effect resulted from a combination of variables such as relatively poor vascular function of the patient, chemical extravasation, allergic skin reactions, venous valves, vascular intima, and diameter stenosis. Sintilimab rarely causes vascular edema only when drug allergic reaction is the underlying factor. As only a few cases of vascular edema caused by Sintilimab have been reported, causes to such a drug-induced vascular edema remained unclear. INTERVENTIONS: The swelling was controlled by an intravenous specialist nurse according to delayed extravasation treatment and the doctor anti-allergy treatment, but the uncertainty of repeated puncture and symptom diagnosis caused pain and anxiety to the patient and his family. OUTCOMES: The symptom of swelling was gradually relieved after the anti-allergic treatment. The patient completed the following drug infusion without discomfort after the third puncture. When the patient was discharged the next day, swelling in his both hands disappeared, and the patient had no anxiety or discomfort. LESSONS: The side effects of immunotherapy may accumulate over time. Early identification and appropriate nursing management are the keys to minimizing patients' pain and anxiety. To effectively treat symptoms, nurses could benefit from quickly identifying the source of swelling.

Construction of model animals to explore intestinal microbiome for detection of breast cancer.

Breast cancer ranks first among female cancers and has become a major public health problem in the current society. More studies indicated that these cancers are related to the change in the gut microbiome that can cause metabolic and immune system disorders in the body. However, there are few studies on the changes in gut microbiome caused by the onset of breast cancer, and the relationship between breast cancer and gut microbiome needs to be further clarified. In this study, we inoculated 4T1 breast cancer cells to induce breast cancer tumorigenesis in mice and collected their feces samples at different stages during this process. These intestinal florae were analyzed using 16S rRNA gene amplicon sequencing, and the results showed that at the phylum level, the ratio of Firmicutes/Bacteroidetes decreased with the development of the tumor; at the family level, the intestinal microbiome had obvious variations of Lachnospiraceae, Bacteroidaceae, Erysipelotrichaceae, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated that decreased abundance of cancer-related signaling pathways. This study elucidated the relationship between breast cancer and intestinal microbiome, and the research results can be used as an important biomarker for the diagnosis of breast cancer.

Further Characterization of Multi-Organ DEARE and Protection by 16,16 Dimethyl Prostaglandin E2 in a Mouse Model of the Hematopoietic Acute Radiation Syndrome.

Survivors of acute radiation exposure suffer from the delayed effects of acute radiation exposure (DEARE), a chronic condition affecting multiple organs, including lung, kidney, heart, gastrointestinal tract, eyes, and brain, and often causing cancer. While effective medical countermeasures (MCM) for the hematopoietic-acute radiation syndrome (H-ARS) have been identified and approved by the FDA, development of MCM for DEARE has not yet been successful. We previously documented residual bone marrow damage (RBMD) and progressive renal and cardiovascular DEARE in murine survivors of H-ARS, and significant survival efficacy of 16,16-dimethyl prostaglandin E2 (dmPGE2) given as a radioprotectant or radiomitigator for H-ARS. We now describe additional DEARE (physiological and neural function, progressive fur graying, ocular inflammation, and malignancy) developing after sub-threshold doses in our H-ARS model, and detailed analysis of the effects of dmPGE2 administered before (PGE-pre) or after (PGE-post) lethal total-body irradiation (TBI) on these DEARE. Administration of PGE-pre normalized the twofold reduction of white blood cells (WBC) and lymphocytes seen in vehicle-treated survivors (Veh), and increased the number of bone marrow (BM) cells, splenocytes, thymocytes, and phenotypically defined hematopoietic progenitor cells (HPC) and hematopoietic stem cells (HSC) to levels equivalent to those in non-irradiated age-matched controls. PGE-pre significantly protected HPC colony formation ex vivo by >twofold, long term-HSC in vivo engraftment potential up to ninefold, and significantly blunted TBI-induced myeloid skewing. Secondary transplantation documented continued production of LT-HSC with normal lineage differentiation. PGE-pre reduced development of DEARE cardiovascular pathologies and renal damage; prevented coronary artery rarefication, blunted progressive loss of coronary artery endothelia, reduced inflammation and coronary early senescence, and blunted radiation-induced increase in blood urea nitrogen (BUN). Ocular monocytes were significantly lower in PGE-pre mice, as was TBI-induced fur graying. Increased body weight and decreased frailty in male mice, and reduced incidence of thymic lymphoma were documented in PGE-pre mice. In assays measuring behavioral and cognitive functions, PGE-pre reduced anxiety in females, significantly blunted shock flinch response, and increased exploratory behavior in males. No effect of TBI was observed on memory in any group. PGE-post, despite significantly increasing 30-day survival in H-ARS and WBC and hematopoietic recovery, was not effective in reducing TBI-induced RBMD or any other DEARE. In summary, dmPGE2 administered as an H-ARS MCM before lethal TBI significantly increased 30-day survival and ameliorated RBMD and multi-organ and cognitive/behavioral DEARE to at least 12 months after TBI, whereas given after TBI, dmPGE2 enhances survival from H-ARS but has little impact on RBMD or other DEARE.

Evaluating Histone Acetylation in Mouse Hematopoietic Stem and Progenitor Cells Using Chromatin Immunoprecipitation.

Epigenetics is the study of how cells control gene activity without changing the DNA sequence. Various epigenetic processes have been identified, including methylation, acetylation, phosphorylation, and ubiquitylation. Epigenetic processes are natural and essential to cell functions; however, when they occur improperly or at the wrong time, adverse effects can occur. A significant epigenetic process is chromatin modification. Chromatin-DNA complexes can be modified by acetylation, altering chromatin structure to influence gene expression. Stresses to hematopoietic stem and progenitor cells, such as ionizing radiation and aging, have significant effects on genomic function. Understanding epigenetic regulation in hematopoietic cells, particularly under stress, offers the potential for therapeutic intervention. We have utilized Chromatin immunoprecipitation (ChIP) in HSPCs to understand epigenetic regulation in response to ionizing radiation. This technique can be applied reliably to rare hematopoietic cells and offers a powerful tool to explore epigenetic regulation in HSPCs.

The mediation and interaction of depressive symptoms in activities of daily living and active aging in rural elderly: A cross-sectional survey.

Background: Compared with urban areas, old adults in rural areas have limited access to medical and health resources in China. Active of daily living ability (ADL) decline and depressive symptoms are common in rural older adults. In particular, the depressive symptoms of the elderly in rural areas are often ignored. Thus, it is difficult to realize high-level active aging at the individual level. In order to explore the effects of ADL and depressive symptoms on the active aging of rural elderly, we conducted a survey and analyzed the mediation and interaction effects of depressive symptoms of ADL on active aging. Methods: From July to November 2019, a cross-sectional study of 945 elderly rural individuals was conducted in three townships in Xiangtan County, China. Active aging, ADL, and depressive symptoms were assessed using the positive aging questionnaire (PAEQ), ADL scale, and depression in old age scale (DIA-S), respectively. PROCESS macro program model 4 and logistic regression were used to explore the mediation and interaction between ADL and depressive symptoms on active aging. Results: The proportions of rural elderly with an active aging level were 23.5% (well above average), 50.9% (above average), 24.1% (below average), 1.5% (well below average), respectively. The rates of ADL decline and depressive symptoms were 44.7 and 19.7%, respectively. Mediated effect analysis showed that the relationship between ADL and active aging could be partly mediated by depressive symptoms (ab = -0.2382, boot SE = 0.0437), and the 95% confidence interval was [-0.3311, -0.1584]. The mediating effect proportion of the total effect was 30.7%. Logistic regression showed that ADL and depressive symptoms have an interactive additive effect on active aging. The relative excess risk of interaction (RERI), the attributable proportion due to interaction (API), and the synergy index (SI) scores were 13.109, 0.621, and 2.871, respectively. Older adults with ADL decline and depressive symptoms had higher (OR = 21.115) odds of well-below-average active aging compared with older adults with ADL decline (OR = 3.258) or only depressive symptoms (OR = 5.749). Conclusion: The findings suggest that the association between ADL and active aging is persistent and partly mediated by depressive symptoms, and comorbid depressive symptoms and ADL decline have an additive effect on active aging. Maintaining independence is an important factor for realizing active aging. However, for the rural elderly with ADL decline and low-level active aging, we can promote the realization of high-level active aging at the individual level through the prevention and treatment of depressive symptoms based on multidisciplinary care.

Antitumor activity of recombinant oncolytic vaccinia virus with human IL2.

The tumor microenvironment is highly immunosuppressive. The genetically modified oncolytic vaccinia virus (OVV) is a promising vector for cancer immunotherapy. The aim of the present study was to assess the antitumor effects of human interleukin-2 (hIL2)-armed OVV in vitro. The hIL2 gene was inserted into a thymidine kinase and the viral growth factor double deleted oncolytic VV (VVDD) to generate recombinant hIL2-armed OVV (rVVDD-hIL2). Viral replication capacity in A549 cells was quantified by plaque titration on CV-1 cells. Production of hIL2 in cancer cells infected by rVVDD-hIL2 was measured by enzyme-linked immunosorbent assay. Finally, 3-(4,5-dimethylthiazol-2-yl)-5-(3-arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to assess the antitumor effects of rVVDD-hIL2. The results showed that rVVDD-hIL2 viral particles expressed increasing levels of hIL2 in human and murine cancer cell lines with growing multiplicities of infection (MOIs). The insertion of the hIL2 gene did not impair the replication capacity of VV, and the rVVDD-hIL2 virus killed cancer cells efficaciously. The lytic effects of the recombinant oncolytic virus on tumor cells increased with the growing MOIs. In conclusion, these findings suggest that hIL2-armed VVDD effectively infects and lyses tumor cells, with high expression of hIL2.

Influencing Factors on College Students' Willingness to Spread Internet Public Opinion: Analysis Based on COVID-19 Data in China.

Following COVID-19 outbreak, Internet public opinion has tended to proliferate. From a theoretical perspective, however, the spread law of Internet public opinion in major epidemic prevention and control may provide optimization strategies on how best to channel Internet public opinion. Specifically, this article aims at exploring key factors affecting our theoretical understanding on the spread of Internet public opinion on a major epidemic situation amongst college students. A questionnaire survey on college students was conducted via online research data collection platform located in Changsha, China, amassing three hundred and nineteen valid questionnaires. Smart PLS was applied to verify a theoretical model vis-à-vis the reliability and validity of the measuring instrument. Results show that adult attachment and social motivation have significant positive influences on the consciousness of social participation. Evidently, adult attachment, emotional orientation and risk perception also have significant positive influences on emotional motivation. Emotional motivation plays a mediating role in the relationship between affective disposition and dissemination willingness. Additionally, social motivation, consciousness of social participation and emotional motivation significantly influence one's dissemination willingness in a positive way. The consciousness of social participation plays a mediating role in the relationship between social motivation and dissemination willingness. Social motivation plays a moderating role in the relationship between risk perception and dissemination willingness. Altogether, theoretical rationalization to enhance understanding and guide the initiation and spread of Internet public opinion of major public health emergencies accurately has now been provided by this work.

Upregulation of SIRT1 Contributes to dmPGE2-dependent Radioprotection of Hematopoietic Stem Cells.

Exposure to potentially lethal high-dose ionizing radiation results in bone marrow suppression, known as the hematopoietic acute radiation syndrome (H-ARS), which can lead to pancytopenia and possible death from hemorrhage or infection. Medical countermeasures to protect from or mitigate the effects of radiation exposure are an ongoing medical need. We recently reported that 16,16 dimethyl prostaglandin E2 (dmPGE2) given prior to lethal irradiation protects hematopoietic stem (HSCs) and progenitor (HPCs) cells and accelerates hematopoietic recovery by attenuating mitochondrial compromise, DNA damage, apoptosis, and senescence. However, molecular mechanisms responsible for the radioprotective effects of dmPGE2 on HSCs are not well understood. In this report, we identify a crucial role for the NAD+-dependent histone deacetylase Sirtuin 1 (Sirt1) downstream of PKA and CREB in dmPGE2-dependent radioprotection of hematopoietic cells. We found that dmPGE2 increases Sirt1 expression and activity in hematopoietic cells including HSCs and pharmacologic and genetic suppression of Sirt1 attenuates the radioprotective effects of dmPGE2 on HSC and HPC function and its ability to reduce DNA damage, apoptosis, and senescence and stimulate autophagy in HSCs. DmPGE2-mediated enhancement of Sirt1 activity in irradiated mice is accompanied by epigenetic downregulation of p53 activation and inhibition of H3K9 and H4K16 acetylation at the promoters of the genes involved in DNA repair, apoptosis, and autophagy, including p53, Ku70, Ku80, LC3b, ATG7, and NF-κB. These studies expand our understanding of intracellular events that are induced by IR but prevented/attenuated by dmPGE2 and suggest that modulation of Sirt1 activity may facilitate hematopoietic recovery following hematopoietic stress. Graphical Abstract.

Influence of leadership empowering behavior on employee innovation behavior: The moderating effect of personal development support.

The main purpose of this study is to explore the influence of leadership empowering behavior (personal development support, participative decision making and delegation of authority) and thriving at work (vigor, learning) on employee innovation behavior and analyze the moderating effect of personal development support on participative decision making and innovation behavior. The questionnaire survey method is used to survey Chinese industrial workers, and a total of 290 valid questionnaires are collected. The model is verified using SmartPLS. Results show that the personal development support and participative decision making dimensions of leadership empowering behavior have a significant positive influence on employee innovation behavior. Vigor and learning has a significant positive influence on employee innovation behavior, and personal development support has a significant moderating effect on the relationship between participative decision making and innovative behavior.

Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors.

The emergence of immune checkpoint inhibitors (ICIs), mainly based on PD-1/PD-L1 blockade has revolutionized the therapeutic landscape of cancer. Despite the huge clinical success ICIs have achieved, about 70% of patients still showed de novo and adaptive resistance. Exploring novel and complementary immune checkpoint molecules in addition to PD-1/PD-L1 is in great urgency. T cell immunoglobulin and ITIM domain (TIGIT) is a co-inhibitory molecule containing an immunoreceptor tyrosine-based inhibition motif (ITIM) within its cytoplasmic tail, and is highly expressed on regulatory T cells and activated CD4+ T, CD8+ T, and NK cells. We generated a novel single chain Fab heterodimeric bispecific IgG antibody format targeting PD-L1 and TIGIT with one binding site for each target antigen. The bispecifc antibody BiAb-1 is based on "knob-into-hole" technology for heavy chain heterodimerization with a glycine serine linker connecting the 3' end of Cκand the 5' end of VH to prevent wrong pairing of light chains. BiAb-1 was produced with high expression yields and show simultaneous binding to PD-L1 and TIGIT with high affinity. Importantly, cytokine production was enhanced by BiAb-1 from staphylococcal enterotoxin B (SEB) stimulated PBMCs. BiAb-1 also demonstrated potent anti-tumor efficacy in multiple tumor models and superior activity to PD-1/PD-L1 blockade molecules. In conclusion, we have applied rational antibody engineering technology to develop a monovalent heterodimeric bispecifc antibody, which combines the blockade of both PD-1/PD-L1 and TIGIT/CD155 pathways simultaneously and results in superior anti-tumor efficacy in multiple tumor models over existing anti PD-1/PD-L1 molecules.

MicroRNA-106a-5p promotes the proliferation, autophagy and migration of lung adenocarcinoma cells by targeting LKB1/AMPK.

It has previously been reported that lung cancer has the highest morbidity and mortality rate worldwide; however, the pathogenesis underlying lung cancer has not been fully elucidated. The aim of the present was primarily to assess the influence of microRNA (miR)-106a-5p on the biological behaviors of lung cancer cells. In the present study, bioinformatics analysis was used to analyze the expression characteristics of miR-106a-5p and its relationship with the prognosis of patients with lung adenocarcinoma (LUAD) in The Cancer Genome Atlas. A dual luciferase reporter assay was performed to verify the binding of miR-106a-5p and liver kinase B1 (LKB1). The Cell Counting Kit-8, colony formation and Transwell assays were utilized to detect cell viability, proliferation and migration, respectively. Protein and RNA expression levels were examined by western blotting and reverse transcription-quantitative PCR analysis, respectively. It was observed that miR-106a-5p was highly expressed in LUAD and associated with poor prognosis. miR-106a-5p promoted the proliferation and migration of LUAD cells, and inhibited autophagy. By contrast, LKB1 inhibited cell proliferation and migration, promoted autophagy and blocked the cancer-promoting effects of miR-106a-5p. Overexpression of miR-106a-5p inhibited the phosphorylation of AMP-activated protein kinase (AMPK) and tuberin (TSC2), and promoted the phosphorylation of mTOR. By contrast, overexpression of LKB1 blocked the promotion of mTOR phosphorylation, and the inhibition of AMPK and TSC2 phosphorylation caused by miR-106a-5p. In summary, the results of the present study indicated that miR-106a-5p regulated the phosphorylation of the AMPK pathway by targeting LKB1, and was involved in the proliferation, migration and autophagy of LUAD cells.

Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma.

Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34+ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 106 CD34+ cells/kg were collected in the first apheresis and 9.2 × 106 CD34+ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 106 in first apheresis and 7.2 × 106/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reduced on CD34+ cells and a higher CD4+/CD8+ T-cell ratio was observed after mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34+ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.

Whole-genome sequencing suggests a role of MIF in the pathophysiology of TEMPI syndrome.

TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell-directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.