Beneficial effects of short-term exposure to indoor biophilic environments on psychophysiological health: Evidence from electrophysiological activity and salivary metabolomics.

BACKGROUND: The utilization of short-term natural exposure as a health intervention has great potential in the field of public health. However, previous studies have mostly focused on outdoor urban green spaces, with limited research on indoor biophilic environments, and the physiological regulatory mechanisms involved remain unclear. OBJECTIVES: To explore the affective and physiological impact of short-term exposure to indoor biophilic environments and their potential regulatory mechanisms. METHODS: A between-group design experiment was conducted, and the psychophysiological responses of participants to the indoor plants (Vicks Plant) were measured by a method combined the subjective survey, electrophysiological measurements, and salivary biochemical analysis. Volatile organic compounds (VOCs) from plants were also detected to analyze the main substances that caused olfactory stimuli. RESULTS: Compared with the non-biophilic environment, short-term exposure to the indoor biophilic environment was associated with psychological and physiological relaxation, including reduced negative emotions, improved positive emotions, lower heart rate, skin conductance level, salivary cortisol and pro-inflammatory cytokines, and increased alpha brainwave power. Salivary metabolomics analysis revealed that the differential metabolites observed between the groups exhibited enrichment in two metabolic pathways related to neural function and immune response: phenylalanine, tyrosine and tryptophan biosynthesis, and ubiquinone and other terpenoid-quinone biosynthesis. These changes may be associated with the combined visual and olfactory stimuli of the biophilic environment, in which D-limonene was the dominant substance in plant-derived VOCs. CONCLUSION: This research demonstrated the benefits of short-term exposure to indoor biophilic environments on psychophysiological health through evidence from both the nervous and endocrine systems.

Prognostic significance of serum monoclonal proteins based on immunofixation electrophoresis in B-cell non-Hodgkin lymphoma.

The presence of serum monoclonal components has been associated with poor outcomes in various hematological malignancies. The current study focused on exploring its prognostic role in B-cell non-Hodgkin lymphoma. Our study represented 314 patients with information on serum immunofixation electrophoresis at diagnosis that were available with B-cell non-Hodgkin lymphoma. IFE was positive in 61 patients (19%). Baseline features were comparable between pairs of groups, poor ECOG PS, B symptoms, advanced stage, and high-risk IPI score were significantly more frequent in the + IFE group. Shorter PFS and OS of B-NHL patients were observed in patients who presented at diagnosis with a + IFE, and IFE was the independent predictor of PFS and OS in multivariate analysis. Moreover, integrating IFE into the IPI-M1, IPI-M2, and IPI-M3 models improved the area under the curve for more accurate survival prediction and prognosis. Serum monoclonal proteins are significant prognostic indicators for newly diagnosed B-cell non-Hodgkin lymphoma that can early identify patients with poor prognosis and guide clinical treatment decisions.

The experience of diagnosis and treatment for TAFRO syndrome.

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important.

Diagnosis of a Rabbit Hemorrhagic Disease Virus 2 (RHDV2) and the Humoral Immune Protection Effect of VP60 Vaccine.

Rabbit hemorrhagic disease (RHD) is known as rabbit plague and hemorrhagic pneumonia. It is an acute, septic, and highly fatal infectious disease caused by the Lagovirus rabbit hemorrhagic disease virus (RHDV) in the family Caliciviridae that infects wild and domestic rabbits and hares (lagomorphs). At present, RHDV2 has caused huge economic losses to the commercial rabbit trade and led to a decline in the number of wild lagomorphs worldwide. We performed a necropsy and pathological observations on five dead rabbits on a rabbit farm in Tai'an, China. The results were highly similar to the clinical and pathological changes of typical RHD. RHDV2 strain was isolated and identified by RT-PCR, and partial gene sequencing and genetic evolution analysis were carried out. There were significant differences in genetic characteristics and antigenicity between RHDV2 and classical RHDV strain, and the vaccine prepared with the RHDV strain cannot effectively prevent rabbit infection with RHDV2. Therefore, we evaluated the protective efficacy of a novel rabbit hemorrhagic virus baculovirus vector inactivated vaccine (VP60) in clinical application by animal regression experiment. The result showed that VP60 could effectively induce humoral immunity in rabbits. The vaccine itself had no significant effect on the health status of rabbits. This study suggested that the clinical application of VP60 may provide new ideas for preventing the spread of RHD2.

CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

[Analysis of Histologic Transformation and Prognosis for Follicular Lymphoma].

OBJECTIVE: To investigate the related factors of invasive transformation and prognosis for follicular lymphoma. METHODS: A total of 168 patients with follicular lymphoma at First Affiliated Hospital of Zhengzhou University from August 2015 to January 2021 were collected, and the significance of each index in histological transformation (HT) and prognosis were analyzed. RESULTS: Pathology grade3, Ki-67 index ≥40%, ß2MG＞3 mg/L, LDH＞245 U/L, POD24 and non-invasion of bone marrow were associated with HT. Univariate analysis showed that the high risk of FLIPI-2, pathological grade 3, Ki-67≥40%, anemia, ß2MG＞3 mg/L, LDH＞245 U/L and HT had significant adverse effects on PFS; ß2MG＞3 mg/L, LDH＞245 U/L, POD24 and HT had significant adverse effects on OS. Cox multivariate analysis showed that the ß2MG >3 mg/L and HT were independent risk factors of PFS, HT was independent risk factor of OS. CONCLUSION: The pathological grade, Ki-67, ß2MG, LDH, POD24 and bone marrow invasion of FL can predict the risk of HT. Meanwhile, ß2MG >3 mg/L and HT are significantly related to poor prognosis of FL.

PARP inhibitor exerts an anti-tumor effect via LMO2 and synergizes with cisplatin in natural killer/T cell lymphoma.

BACKGROUND: PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL. METHODS: The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo. RESULTS: PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo. CONCLUSIONS: In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.

Enhanced efficacy of combined fluzoparib and chidamide targeting in natural killer/T-cell lymphoma.

The treatment of natural killer/T-cell lymphoma (NKTCL) presents an onerous challenge, and a search for new therapeutic targets is urgently needed. Poly ADP-ribose polymerase inhibitors (PARPi) were initially used to treat breast and ovarian cancers with BRCA1/2 mutations. Their excellent antitumor efficacy led to a series of clinical trials conducted in other malignancies. However, the exploration of PARPi and their potential use in combination treatments for NKTCL remains unexplored. We treated NKTCL cell lines with fluzoparib (a novel inhibitor of PARP) and chidamide (a classical inhibitor of HDACs) to explore their cytotoxic effects in vitro. Then, their antitumor efficacy in vivo was confirmed in YT-luciferin xenograft mouse models. Fluzoparib or chidamide alone inhibited NKTCL cell proliferation in a dose-dependent manner. Cotreatment with both drugs synergistically induced excessive accumulation of DNA double-strand breaks and massive apoptotic cell death by inhibiting the DNA damage repair pathway, as shown by the decreased protein levels of p-ATM, p-BRCA1, p-ATR, and Rad51. Moreover, the combination treatment apparently increased the level of intracellular reactive oxygen species (ROS) to enhance apoptosis, and pretreatment with an ROS scavenger reduced the proapoptotic effect by 30-60% in NKTCL cell lines. In vivo, this combined regimen also showed synergistic antitumor effects in xenograft mouse models. The combination of fluzoparib and chidamide showed synergistic effects against NKTCL both in vitro and in vivo and deserves further exploration in clinical trials.

T-cell dysfunction in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity.

A second-generation CD38-CAR-T cell for the treatment of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T-cell therapy has been a promising immunotherapy against hematological malignancies. METHODS: In this study, we developed a second-generation CAR construct and generated CAR-T cells targeting CD38 molecule. Then effects of CAR-T cells against MM cell lines were evaluated. RESULTS: CD38-CAR-T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR-T cells even at effector to target ratio of 1:100. CAR-T cells also showed an enhanced cytotoxicity against primary MM cells. CAR-T cells could be activated and produced a variety of cytokines in a target-dependent manner. In vivo test indicated that CAR-T cells also showed significant antitumor effect on xenograft mice models. CONCLUSION: These results indicated a promising therapeutic strategy of CD38-CAR-T cells against MM.

Chinese young people's perceptions and preferences with regard to various edible urban plants. / 中国年轻人对各种可食用城市植物的看法和偏好.

The World Health Organization (WHO) defines health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity" (WHO, 2017), and mental health is defined as not only the absence of mental illness, but also the presence of psychological well-being. An expanding body of evidence highlights the relationship between nature (such as urban greenspace) and health (Li et al., 2019; Flaxman et al., 2020). However, human development and subsequent effects such as climate change and epidemic disease (COVID-19) lead to altered living environments and lifestyles. Expanding cities and urban residents have inequitable access to nature, particularly in areas of greater depriv­ation, where both public and private greenspaces are less available (Feng et al., 2021). In addition, young people spend more than 80% of their time indoors due to constant use of electronic devices for work, study, and entertainment (Klepeis et al., 2001). Mobile phones, personal computers, and video-game devices have become the main means for them to release stress. Excessive use of these electronic devices may affect normal brain activity, increasing the risk of Internet addiction and producing a range of physical and mental problems (Tran et al., 2017). These signal the pressing need for scientific investigation of efficient and convenient ways to increase contact with nature, or alternatively, to better regulate emotions indoors.

Emerging roles of the gut microbiota in cancer immunotherapy.

Gut microbiota represents a hidden treasure vault encompassing trillions of microorganisms that inhabit the intestinal epithelial barrier of the host. In the past decade, numerous in-vitro, animal and clinical studies have revealed the profound roles of gut microbiota in maintaining the homeostasis of various physiological functions, especially immune modulation, and remarkable differences in the configuration of microbial communities between cancers and healthy individuals. In addition, although considerable efforts have been devoted to cancer treatments, there remain many patients succumb to their disease with the incremental cancer burden worldwide. Nevertheless, compared with the stability of human genome, the plasticity of gut microbiota renders it a promising opportunity for individualized treatment. Meanwhile, burgeoning findings indicate that gut microbiota is involved in close interactions with the outcomes of diverse cancer immunotherapy protocols, including immune checkpoint blockade therapy, allogeneic hematopoietic stem cell transplantation, and chimeric antigen receptor T cell therapy. Here, we reviewed the evidence for the capacity of gut microflora to modulate cancer immunotherapies, and highlighted the opportunities of microbiota-based prognostic prediction, as well as microbiotherapy by targeting the microflora to potentiate anticancer efficacy while attenuating toxicity, which will be pivotal to the development of personalized cancer treatment strategies.

Synergistic anticancer effect of a combination of chidamide and etoposide against NK/T cell lymphoma.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive hematological malignancy. However, there is currently no consensus on therapies for refractory/relapsed patients. In this study, we investigated the synergistic anticancer effect and potential mechanism of combining chidamide, a histone deacetylases (HDACs) inhibitor, and etoposide, a DNA-damaging agent, in NKTCL. We demonstrated that chidamide or etoposide alone dose- and time-dependently inhibited the cell viability of NKTCL cell lines, YT, NKYS and KHYG-1. Functional experiments suggested that combined chidamide and etoposide treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic death in vitro and in vivo. Furthermore, the expression of DNA damage related proteins was detected and we also examined the alternations in histone acetylation, cell cycle progression, and mitochondrial membrane potential (MMP). The results suggested that increased histone acetylation, cell cycle arrest at the G2/M phase and loss of MMP, converging to greater DNA damage, might account for the synergism of the combination of chidamide and etoposide in NKTCL. Taken together, our study provides an evident for possible application on combining HDACs inhibitors and DNA-damaging agents for the treatment of NKTCL.

Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

Preclinical and clinical studies of CAR-NK-cell therapies for malignancies.

The development of chimeric antigen receptor T (CAR-T) cell therapy, a specific type of immunotherapy, in recent decades was a fantastic breakthrough for the treatment of hematological malignancies. However, difficulties in collecting normal T cells from patients and the time cost of manufacturing CAR-T cells have limited the application of CAR-T-cell therapy. In addition, the termination of related clinical trials on universal CAR-T cell therapy has made further research more difficult. Natural killer (NK) cells have drawn great attention in recent years. Chimeric antigen receptor-NK (CAR-NK) cell therapy is a promising strategy in the treatment of malignant tumors because of its lack of potential for causing graft-versus-host disease (GVHD). In this review, we will address the advances in and achievements of CAR-NK cell therapy.

The clinical characteristics and prognostic factors of 410 patients with natural killer/T-cell lymphoma.

PURPOSE: To investigate the clinical characteristics and prognostic factors of natural killer/T-cell lymphoma (NKTCL). METHODS: We retrospectively reviewed 410 NKTCL patients admitted to our lymphoma center from 2000 to 2019. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method, and the differences between the study groups were compared by the log-rank test. RESULTS: The median age of the 410 patients was 44 (range 8-84), and the 5-year OS and PFS were 61.2% and 38.4%, respectively. For patients with stage I/II, the 5-year PFS rate was 57.5%, and the 5-year OS rate was 77.2%. For patients with stage III/IV, the 5-year PFS rate was 17.4%, and the 5-year OS rate was 43.7%. Compared to the patients who received radiotherapy alone or chemotherapy alone as their initial treatment, the patients who received combined chemoradiotherapy had longer PFS (P = 0.013). Independent prognostic factors for OS were stage III/IV (P = 0.001), elevated IPI/aaIPI score (P = 0.019), elevated PINK score (P < 0.001) and elevated plasma EBV-DNA (P = 0.003). An elevated PINK score (P < 0.001) was an independent prognostic factor for PFS. CONCLUSION: Stage III/IV, elevated IPI/aaIPI score, elevated PINK score and elevated plasma EBV-DNA were independent prognostic factors for OS. Elevated PINK score was an independent prognostic factor for PFS. In stage III/IV patients, the patients who received combined chemoradiotherapy had significantly longer PFS.