Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

Objective: To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. Methods and analysis: The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Results: Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Conclusion: Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

Design and simulation of a near-infrared enhanced Si-based SPAD for an automotive LiDAR.

A near-infrared (NIR)-enhanced single-photon avalanche diode (SPAD) with a retrograded NM/XP junction for an automotive LiDAR was designed based on CSMC 0.18 µm BCD technology. A 3 µm depth NM/XP junction embedded in a lightly doped deep p-well (DP) improves the absorption efficiency in the NIR regime; the photo-generated electrons generated in the depletion region are efficiently collected into the central multiplication region by a drift process, and then the impact ionization is triggered by the strong field, resulting in a high photon detection efficiency (PDE). Additionally, the deep NM/XP junction and the buried layer effectively isolate the dark noise originating from the interface and the substrate. The SPAD was initially simulated by numerical calculation, and then was evaluated with active quench/reset electronics in a circuit simulator. The results revealed that the SPAD with an active area of 314µm 2 achieves a PDE of 16.2% at 905 nm and a dark count rate (DCR) of 1.46H z/µm 2, with an excess bias of 5 V at room temperature. The designed SPAD is well suited for the low-cost, miniaturized automotive LiDAR.

Neoadjuvant therapy for HER2-positive acantholytic squamous cell breast carcinoma: a case report.

HER2-positive acantholytic squamous cell carcinoma (ASCC) of the breast is exceptionally rare, and its clinicopathologic features are poorly understood. The impact of neoadjuvant therapy on HER2-positive breast ASCC is unclear. Here we report on a 58-year-old woman who was diagnosed with HER2-positive ASCC of the right breast, who underwent neoadjuvant treatment with albumin-paclitaxel, carboplatin, and trastuzumab, and surgery. Neoadjuvant therapy was effective, with no recurrence or metastasis after 1.5 years of postoperative follow-up.

A novel ternary deep eutectic solvent pretreatment for the efficient separation and conversion of high-quality gutta-percha, value-added lignin and monosaccharide from Eucommia ulmoides seed shells.

A novel ternary deep eutectic solvent (DES), consisted of choline chloride, oxalic acid and ethylene glycol, was developed as a green, low-cost and recyclable pretreatment system for multi-stage utilization of Eucommia ulmoides seed shells. Under optimum conditions, 79.7 % hemicellulose and 65.6 % lignin were quickly removed while 84.0 % cellulose was retained. After DES pretreatment, the yield and purity of gutta-percha achieved 85.1 mg/g and 96.2 %, which increased 1.4 and 1.8 folds higher than that of un-treatment ones. Meanwhile, 69.1 % enzymatic digestibility of cellulose was obtained, that was 2.3 folds higher than that of raw substrates. Moreover, 53.6 % low-condensation lignin with aromatic structures and valuable aryl-ether linkages was well collected. Importantly, the DES that has been recycled five runs can still remove 73.9 % hemicellulose and 58.0 % lignin. Overall, the DES was determined to efficiently promote the separation and conversion of high-quality gutta-percha, value-added lignin and high-yield glucose from Eucommia ulmoides seed shells.

Natural variation of ZmLNG1 alters organ shapes in maize.

The development of a series of elite maize hybrids has greatly increased crop yield in the past decades. Parental lines of these hybrids usually come from different heterotic groups and contain many genetic differences. Identifications of important quantitative trait genes in the elite hybrids can extend our understanding of heterosis and also help to guide genetic improvement. Here, we mapped a major quantitative trait locus using a linkage population from an elite maize hybrid Zhengdan958 and identified ZmLNG1 as the causative gene controlling multiple morphologic traits in maize. A 6-kb deletion in one parental line of the hybrid leads to the fusion of ZmLNG1 with its nearby gene. The fusion event prevents the C-terminal of ZmLNG1 from interacting with ZmTON1, which resulted in the change of plant architecture. Further experiments demonstrated that ZmLNG1 could act as a mediator to connect ZmTON1 and ZmOFPs, which belong to another type of plant morphological regulatory proteins, thereby affecting the phosphorylation level of ZmOFPs. These results demonstrate the importance of ZmLNG1 in forming the TON1-TRM-PP2A complex and provide a model for the regulation of plant organ morphology by TON1-recruiting motifs (TRMs) and Ovate family proteins (OFPs).

Targeted therapy of atherosclerosis by pH-sensitive hyaluronic acid nanoparticles co-delivering all-trans retinal and rapamycin.

Atherosclerosis, the leading cause of death in the elderly worldwide, is typically characterized by elevated reactive oxygen species (ROS) levels and a chronic inflammatory state at the arterial plaques. Herein, pH-sensitive nanoparticles (HRRAP NPs) co-delivering all-trans retinal (ATR), an antioxidant linked to hyaluronic acid (HA) through a pH-sensitive hydrazone bond, and rapamycin (RAP), an anti-atherosclerotic drug loaded into the nanoparticle core, are developed for targeted combination therapy of atherosclerosis. In this way, HRRAP NPs might simultaneously reduce ROS levels via ATR antioxidant activity and reduce inflammation via the anti-inflammatory effect of RAP. In response to mildly acidic conditions mimicking the lesional inflammation in vitro, HRRAP NPs dissociated and both ATR and RAP were effectively released. The developed HRRAP NPs effectively inhibited pro-inflammatory macrophage proliferation, and displayed dose- and time-dependent specific internalization by different cellular models of atherosclerosis. Also, HRRAP NP combination therapy showed an efficient synergetic anti-atherosclerotic effect in vitro by effectively inhibiting the inflammatory response and oxidative stress in inflammatory cells. More importantly, HR NPs specifically accumulated in the atherosclerotic plaques of apolipoprotein E-deficient (ApoE-/-) mice, by active interaction with HA receptors overexpressed by different cells of the plaque. The treatment with HRRAP NPs remarkably inhibited the progression of atherosclerosis in ApoE-/- mice which resulted in stable plaques with considerably smaller necrotic cores, lower matrix metalloproteinase-9, and decreased proliferation of macrophages and smooth muscle cells (SMCs). Furthermore, HRRAP NPs attenuated RAP adverse effects and exhibited a good safety profile after long-term treatment in mice. Consequently, the developed pH-sensitive HRRAP NP represent a promising nanoplatform for atherosclerosis combination therapy.

The Role of Twitter Medium in Business with Regression Analysis and Statistical Modelling.

Marketing refers to the strategies a company undertakes to promote its brands to its potential audience. Advertising provides useful venues for marketing to promote a company's survives/goods to the audience. It has a positive impact on the sale of services or products. In this study, we consider a well-known online medium called Twitter (the fourth most popular social media platform used by marketers) to check its impact on sales. For this purpose, the simple linear regression modeling approach is implemented to test the significance and usefulness of Twitter advertising on sale. Statistical tests such as t-test and correlation test are adopted to test the hypothesis of the "impact of Twitter advertising on sales." Based on the findings of this study, it is observed that Twitter advertising has a positive impact on sales. Furthermore, a new statistical model called the exponential T-X exponentiated exponential is introduced. The proposed model is very interesting and possesses heavy-tailed characteristics which are useful in finance and other related sectors. Finally, the applicability of the new model is illustrated by considering the sales data.

Autophagy promotes oncolysis of an adenovirus expressing apoptin in human bladder cancer models.

As a potential cancer therapy, we developed a recombinant adenovirus named Ad-VT, which was designed to express the apoptosis-inducing gene (apoptin) and selectively replicate in cancer cells via E1a manipulation. However, how it performs in bladder cancer remains unclear. We examined the antitumor efficacy of Ad-VT in bladder cancers using CCK-8 assays and xenograft models. Autophagy levels were evaluated by western blotting, MDC staining, and RFP-GFP-LC3 aggregates' analyses. Here, we report the selective replication and antitumor efficacy (viability inhibition and apoptosis induction) of Ad-VT in bladder cancer cells. Using xenograft tumor models, we demonstrate that its effects are tumor specific resulting in the inhibition of tumor growth and improvement of the survival of mice models. Most Importantly, Ad-VT induced a complete autophagy flux leading to autophagic cancer cell death through a signaling pathway involving AMPK, raptor and mTOR. Finally, we suggest that treatment combination of Ad-VT and rapamycin results in a synergistic improvement of tumor control and survival compared to monotherapy. This study suggests that Ad-VT can induce selective autophagic antitumor activities in bladder cancer through the AMPK-Raptor-mTOR pathway, which can be further improved by rapamycin.

Using etoposide + dexamethasone-based regimens to treat nasal type extranodal natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

PURPOSE: Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) can be associated with hemophagocytic lymphohistiocytosis (NK/T-LAHLH), which is a rare and fatal disease with no effective therapy. We evaluated whether etoposide + dexamethasone-based chemotherapy regimens might be useful for treating NK/T-LAHLH. METHODS: This retrospective single-center study evaluated clinical data from 37 patients with NK/T-LAHLH who were treated between May 2008 and January 2020. RESULTS: Among 363 patients with ENKTL, the cumulative incidence of HLH was 11.9%. Among 43 patients with NK/T-LAHLH, 37 patients received etoposide + dexamethasone-based chemotherapy regimens, with an overall response rate of 45.9% for the HLH. The overall response rate was substantially higher for newly diagnosed NK/T-LAHLH than it was for relapsed or refractory NK/T-LAHLH (66.7% vs. 18.8%). The median overall follow-up time was 4 months, with overall survival rates of 81.1% at 1 month, 62.2% at 2 months, 56.8% at 3 months, and 34.4% at 6 months. Significantly better overall survival (all P < 0.05) was observed for patients with newly diagnosed NK/T-LAHLH (vs. relapsed/refractory disease), stage I/II disease (vs. stage III/IV disease), and nasal disease (vs. non-nasal disease). Patients who responded to the ENKTL treatment also experienced response in their HLH; 8 patients experienced continued complete response for both HLH and ENKTL. Multivariate analysis revealed that a poor prognosis among patients with NK/T-LAHLH was independently related to relapsed/refractory ENKTL and non-nasal disease. CONCLUSION: Although patients with NK/T-LAHLH generally experienced poor outcomes, etoposide + dexamethasone-based chemotherapy regimens were associated with good outcomes among select patients with newly diagnosed or stage I/II NK/T-LAHLH.

Outcomes of patients treated with SVILE vs. P-GemOx for extranodal natural killer/T-cell lymphoma, nasal type: a prospective, randomized controlled study.

Objective: To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma, nasal type (ND-ENKTL). Methods: From April 2015 to July 2018, 103 patients with ND-ENKTL were randomly assigned to SVILE (experimental group) or P-GemOx (control group) chemotherapy followed by radiotherapy and consolidation chemotherapy. The primary endpoint was the overall response rate after 3 cycles of chemotherapy, and secondary study endpoints were complete response (CR), progression-free survival (PFS), and overall survival (OS). Safety was also evaluated. Results: There were no significant differences in baseline characteristics in the experimental vs. control groups. In experimental and control groups, respectively, the overall response rates were 91.7% vs. 97.0% for stage I/II and 75.0% vs. 72.2% for stage III/IV. The CR rates were 83.4% vs. 97.0% for stage I/II and 68.8% vs. 61.1% for stage III/IV. None of those differences were significant. There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV. The 3-year PFS and OS in stage I/II were 88.3% vs. 93.3% and 88.8% vs. 97.0%, respectively. The 3-year PFS and OS in stage III/IV were 46.2% vs. 65.7% and 68.8% vs. 72.2%, respectively. The common adverse events were hematological toxicity, hepatotoxicity, and coagulation abnormalities, which were found to be reversible with supportive therapy. Conclusions: The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated. SVILE is a therapeutic option for ND-ENKTL.

SVILE regimen, a combination of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide, for treating relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type.

OBJECTIVE: To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL). METHODS: This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed. RESULTS: After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage Ⅰ/Ⅱ patients had CR rate of 100.0 % and stage Ⅲ/Ⅳ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage Ⅰ/Ⅱ patients and stage Ⅲ/Ⅳ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P ＜ 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity. CONCLUSIONS: The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.

Treatment outcomes and prognostic analysis of elderly patients with extranodal natural killer/T-cell lymphoma, nasal type: a retrospective analysis.

We retrospectively analyzed the treatment outcomes of elderly patients (aged ≥ 60 years) with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) and investigated the prognostic factors. Fifty-two elderly patients received chemotherapy alone, radiotherapy alone, or chemotherapy followed by radiotherapy ± consolidation chemotherapy as induction therapy. Overall, 97.26% patients in stage I/II had overall response (OR) and 86.1% had complete response (CR), whereas 71.4% of patients in stage III/IV had OR and 35.7% had CR. The 3-year freedom from progression (FFP) rate and overall survival (OS) rate of patients with stage I/II were 78.2% and 85.0%, respectively, and those with stage III/IV were 23.3% and 33.3%. Following multivariate analysis of Cox regression, ECOG performance status scores of 3-4 and stage III/IV were independent prognostic factors for elderly ENKTL patients. Elderly patients with stage I/II or stage III/IV and good or poor performance status can benefit from the commonly used or personalized treatment.

Long-term outcomes of patients treated with an EPOCHL regimen as first-line chemotherapy for newly diagnosed extranodal natural killer/T-cell lymphoma: a retrospective single-center study.

We retrospectively evaluated the long-term outcomes of patients receiving an EPOCHL (EPOCH + L-asparaginase) regimen as first-line chemotherapy for newly diagnosed extranodal natural killer/T cell lymphoma, nasal type (ENKTL). Ninety-six patients received 2-8 cycles of EPOCHL. After 2-4 cycles, 55.2% patients had complete response (CR) and 39.6% had partial response (PR). 42.7% patients developed progressive or relapsed disease. The 5-year progression-free survival (PFS) rates were 56.1% overall, 59.8% for stage I/II, and 34.9% for stage III/IV disease, and corresponding 5-year overall survival (OS) rates were 58.7, 65.3, and 39.8%, respectively. OS differed significantly between patients with stage I/II and those with stage III/IV disease (p = 0.018). Patients who achieved CR had better 3-year OS of 92.9%. Advanced stage disease was a poor prognostic factor for OS. All major adverse events associated with the EPOCHL regimen were reversible, and this first-line chemotherapy was safe and effective for patients with ENKTL.

Synthetic Lipopeptide Enhances Protective Immunity Against Helicobacter pylori Infection.

Over fifty percent of the people around the world is infected with Helicobacter pylori (H. pylori), which is the main cause of gastric diseases such as chronic gastritis and stomach cancer. H. pylori adhesin A (HpaA), which is a surface-located lipoprotein, is essential for bacterial colonization in the gastric mucosa. HpaA had been proposed to be a promising vaccine candidate against H. pylori infection. However, the effect of non-lipidated recombinant HpaA (rHpaA) to stimulate immune response was not very ideal, and the protective effect against H. pylori infection was also limited. Here, we hypothesized that low immunogenicity of rHpaA may attribute to lacking the immunostimulatory properties endowed by the lipid moiety. In this study, two novel lipopeptides, LP1 and LP2, which mimic the terminal structure of the native HpaA (nHpaA), were synthesized and TLR2 activation activity was confirmed in vitro. To investigate whether two novel lipopeptides could improve the protective effect of rHpaA against the infection of H. pylori, groups of mice were immunized either intramuscularly or intranasally with rHpaA together with LP1 or LP2. Compared with rHpaA alone, the bacterial colonization of the mice immunized with rHpaA plus LP2 via intranasal route was significantly decreased and the expression levels of serum IgG2a, IFN-γ, and IL-17 cytokines in spleen lymphocyte culture supernatant increased obviously, indicating that the enhanced protection of LP2 may be associated with elevated specific Th1 and Th17 responses. In conclusion, LP2 has been shown to improve the protective effect of rHpaA against H. pylori infection, which may be closely related to its ability in activating TLR2 by mimicking the terminal structure of nHpaA.

The mucosal adjuvant effect of plant polysaccharides for induction of protective immunity against Helicobacter pylori infection.

Some plant polysaccharides (PPSs) had been used as the adjuvants for systemic vaccination. In this study, we investigated whether PPSs could exhibit adjuvant effect at the mucosa. Groups of mice were intranasally immunized with Epimedium Polysaccharide (EPS), Trollius chinensis polysaccharide (TCPS), Siberian solomonseal rhizome polysaccharide (SSRPS) and Astragalus polysaccharides (APS) together with ovalbumin (OVA). Significantly higher levels of OVA-specific IgG in serum and secretory IgA in saliva, vaginal wash and intestinal lavage fluid were induced after immunization with OVA plus one of the four PPSs compared to OVA alone. Antigen absorption and TLR2 (Toll-like receptor 2) activation may be related to their mucosal adjuvant effect. Of note, when APS used as an adjuvant, intranasally vaccination with recombination UreB (rUreB, Urease subunit B) conferred more robust protection against Helicobacter pylori (H. pylori). Immunized with rUreB in combination APS resulted in mixed specific Th1 and Th17 immune response, which may contribute to the inhibition of H. pylori colonization. Though specific Th2-dominant responses were elicited when the other three PPS intranasally immunized with rUreB, no significant difference in the protective effect were found between those groups and rUreb alone group. Taken together, the four PPSs may be promising candidates for mucosal adjuvant, and APS could enhance rUreB-specific protective immunity against H. pylori infection.

Autologous hematopoietic stem cell transplantation may improve long-term outcomes in patients with newly diagnosed extranodal natural killer/T-cell lymphoma, nasal type: a retrospective controlled study in a single center.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare disease with a poor prognosis. The long-term effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on ENKTL has been reported occasionally but needs further investigation. In this retrospective study from a single center, 20 ENKTL patients who received induction chemotherapy followed by auto-HSCT ± involved-field radiotherapy (IFRT) ± additional chemotherapy were enrolled as a study group. Another 60 fit ENKTL patients who received induction chemotherapy ± IFRT ± additional chemotherapy were selected as the control group. Baseline characteristics of all patients were well balanced. Our analysis showed that after a median follow-up time of 61.0 months (95% CI 52.3-69.7), the auto-HSCT treated group showed better overall survival (OS) than the control group (p = 0.045). The median OS of the auto-HSCT-treated group was not reached, but that of the control group was 62.0 months. Five-year comparison of OS between the two groups also showed a significant difference (79.3 vs. 52.3%, p = 0.026). We suggest that auto-HSCT treatment, in combination with chemoradiotherapy, may prolong OS and improve the long-term outcomes of fit patients with ENKTL compared to treatment with chemoradiotherapy alone.

Very-Low-Dose Decitabine Is Effective in Treating Intermediate- or High-Risk Myelodysplastic Syndrome.

Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.

Septicemia and pneumonia due to Mycobacterium fortuitum infection in a patient with extronodal NK/T-cell lymphoma, nasal type: A case report.

RATIONALE: Mycobacterium fortuitum (M.fortuitum) is one of the rapidly growing nontuberculous mycobacterium (NTM) that is widespread in the environment. M.fortuitum can cause different types of disease including pulmonary disease, lymphadenitis, cutaneous disease, and disseminated disease. However, the infection presenting as septicemia is exceedingly rare. PATIENT CONCERNS: A 48-year-old immunocompromised male with extranodal NK/T-cell lymphoma, nasal type was admitted to the hospital because of high fever for 10 days. DIAGNOSES: The pathogen identified twice in the hemoculture was M.fortuitum, but not in the sputum culture. The chest computed tomographic (CT) scan showed a chronic inflammatory infection. INTERVENTIONS: The patient was treated with sulfamethoxazole and levofloxacin. OUTCOMES: The symptom of patient disappeared after the treatment for one week, and near-total absorption of the consolidation in CT after the treatment for one month. He continued the treatment for one year until the last negative hemoculture. LESSONS: Although the M.fortuitum infection presenting as septicemia is rare, a high suspicion of M.fortuitum is required, particularly in the immunosuppressive patients. Timely and adequate treatment is necessary.