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Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. Methods: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), β-C-terminal telopeptide of type I collagen (β-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. Results: The area under the curve (AUC) predicted by β-C-terminal telopeptide of type I collagen (β-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p

Objectives This study aims to assess the impact of the nationwide Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD), focusing on the clinical characteristics of PCD patients with COVID-19 and the risk factors contributing to adverse clinical courses (severity and hospitalization) and outcomes.Methods A multicenter retrospective study was performed from December 1, 2022, to January 19, 2023. The study population includes 404 PCD patients, divided into a COVID-19 group (n = 342) and an uninfected group (n = 62).Results The frequency of COVID-19 infection was 84.7% (342/404), and 16.4% (56/342) were severe COVID-19. Among the 277 patients with complete follow-up, 2 deaths (0.7%) were reported, while 231 (83.4%) recovered from COVID-19. Age > 65 (P = 0.02) and prior anti-CD38 monoclonal antibody (mAb) treatment within six months (P = 0.03) were independent risk factors for severe infection. Additionally, previous chimeric antigen receptor T-cell (CAR-T) therapy within six months was correlated with a higher risk of hospitalization (P = 0.04) and prolonged recovery time (P = 0.03). No significant protective effect of vaccination on infection or severe infection was observed (P > 0.05).Conclusions The latest Omicron outbreak results in higher rates of severe infection and mortality in PCD patients compared with the general population in China, highlighting the need to protect this vulnerable population during the pandemic. Recent use of anti-CD38 mAb and CAR-T therapy are associated with poorer clinical courses and outcomes of PCD patients with COVID-19.

Background: Studies about the combined effects of gaseous air pollutants and particulate matters are still rare. Objectives: This study was performed based on baseline survey of the Diverse Life-Course Cohort in the Beijing-Tianjin-Hebei (BTH) Region of North China to evaluate the association of long-term air pollutants with blood pressure and the combined effect of the air pollutants mixture among 32821 natural han population aged 20 years or above. Methods: Three-year average exposure to air pollutants (PM10, PM2.5, PM1, O3, SO2, NO2, and CO) and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3−), sulfate (SO42−), and organic matter (OM)] of residential areas were calculated based on well-validated models. Generalized linear mixed models (GLMMs) were used to estimate the associations of air pollutants exposure with the systolic blood pressure (SBP), diastolic blood pressure (DBP), Mean arterial pressure (MAP), pulse pressure (PP) and prevalent hypertension. Quantile g-Computation and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined effect of the air pollutant mixture. Results: We found that long-term exposures of O3, PM2.5, and PM2.5 components were stably and strongly associated with elevated SBP, DBP, and MAP and prevalent hypertension. O3 increased SBP, DBP, and MAP at a similar extent, but with greater effects; while, PM2.5 and PM2.5 components had a greater impact on SBP than DBP, which increased PP simultaneously. In multi-pollutant models, the combined effects of the air pollutant mixture on blood pressure and prevalent hypertension was predominantly influenced by O3, PM2.5, and O3, OM in different models, respectively. For example, O3, PM2.5 contributed 57.25 %, 39.22 % of the positive combined effect of the air pollutant mixture on SBP; and O3, OM positively contributed 70.00 %, 30.00 % on prevalent hypertension, respectively. There were interactions between O3, CO, SO2 and PM2.5 components on hbp, SBP and PP. Conclusions: The results showed positive associations of air pollutant mixtures with blood pressure, where O3 and PM2.5 (especially OM) might be primary contributors. There were interactions between gaseous air pollutants and PM2.5 components on blood pressure and prevalent hypertension.

Abstract Introduction Although the combination of venetoclax (VEN) and hypomethylating agents (HMAs) results in impressive efficacy in acute myeloid leukemia (AML), there is still a subset of patients who are refractory. We investigated the outcomes of AML patients with monocytic differentiation who were treated with frontline VEN/HMA. Methods A total of 155 patients with newly diagnosed AML treated with frontline VEN/HMA were enrolled in the study. Monocyte‐like AML was identified by flow cytometry with typical expression of monocytic markers, and M5 was identified according to French, American, and British category. We compared the outcomes of patients with different characteristics. Results The rate of complete remission (CR) and CR with incomplete recovery of blood counts (CRi), progression‐free survival (PFS), and overall survival (OS) in monocyte‐like AML were inferior to those in nonmonocyte‐like AML (CR/CRi rates, 26.7% vs. 80.0%, p

Abstract Background Comparative investigations evaluating the efficacy of pomalidomide‐based (Pom‐based) versus daratumumab‐based (Dara‐based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real‐world studies. Methods This retrospective cohort study included 140 RRMM patients treated with Pom‐based or Dara‐based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. Results The overall response rates (ORR) for Pom‐based (n = 48), Dara‐based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression‐free survival (PFS) was 5.7 months (95% CI: 5.0–6.5) for the Pom‐based group, 10.5 months (5.2–15.8) for the Dara‐based group, and 6.7 months (4.0–9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara‐based vs. Pom‐based, DPd vs. Pom‐based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double‐refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara‐based regimens over Pom‐based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara‐based and DPd regimens (Pom‐based 39.6% vs. Dara‐based 64.7% vs. DPd 70.8%, p = 0.009). Conclusions In real‐world settings, Pom‐based, Dara‐based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara‐based therapy yielded superior clinical response and PFS compared to Pom‐based therapy.

Abstract With the development of recycled aggregate concrete (RAC), the recovery rate of construction waste is improved, and the pollution problem is alleviated. In particular, RAC beams strengthened with prestressed carbon fiber reinforced plastics (CFRP) can exhibit improved mechanical properties, expanding RAC application. Four groups of reinforced RAC beam specimens contained 0%, 40%, 70%, and 100% recycled coarse aggregate, respectively. Each group of beams was first pre-cracked and then strengthened by prestressed CFRP with one layer and two layers respectively. Finally, the bearing capacity tests were performed for these beams. The test results show that as the recycled coarse aggregate content increases, the cracking moment and ultimate load capacity of the beam decrease, while its crack width increases. As the CFRP layer increases, the deformation and crack width of the beam decreases, while the number of cracks increases. The prestressed CFRP also exhibited tensile and peeling failure. A beam deflection calculation model was established by introducing a coefficient k representing the interaction between recycled aggregate and CFRP. The influence coefficient of concrete elongation on the crack width and average crack spacing of the beam was modified, and the crack width analysis model of the beam was established. The calculated results are in good agreement with the experimental observations. It can provide reference for the application and design of recycled concrete beams strengthened with prestressed CFRP.

Abstract Background In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. Methods Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. Results Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. Conclusions Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. Trial registration This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

The low frequency oscillations that are raised by the interactions between the voltage source converter (VSC) and the weak grid, are becoming a critical threat to power system stability. Identifying the proper parameters for VSC is essential for preventing the appearance of oscillation in advance. To achieve this target, this paper proposes a quantitative evaluation method for the system’s stability to clarify the stable boundary of current control parameters. Then, an active damping controller is proposed and supplemented in the control of VSC, to expand the stable boundary of current control parameters. Thus, the VSC can stably operate within a wider range of parameters selection, the oscillation can be damped without weakening the dynamic control capability of the VSC. The simulation tests are performed to verify the correctness of the quantitative evaluation method and the effectiveness of the proposed stability boundary expansion control.

Abstract Objective Non‐small‐cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). Methods and Results In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid‐2‐related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. Conclusion This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.

Abstract Background Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression. Methods The tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction. Results The results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b. Conclusions Our study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology. Graphical Abstract

Abstract Choroidal neovascularization (CNV) occurs in neovascular age-related macular degeneration (AMD) and often leads to permanent visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the gold standard for the treatment of CNV. However, anti-VEGF treatment did not always cause vision improvement and sometimes had detrimental effects on normal retinal tissues. Herein, we identified a novel retinoic acid drug, EYE-502, which had great therapeutic effects on CNV. Administration of EYE-502 could inhibit VEGF-induced dysfunction of endothelial cells (ECs) and reduce platelet-derived growth factor (PDGF)-induced recruitment of pericytes to ECs in vitro. Administration of EYE-502 could reduce the area of choroidal sprouting and laser-induced CNV, exhibiting similar anti-angiogenic effects as aflibercept. Moreover, administration of EYE-502 could reduce pericyte coverage in the sprouting vessels and choroidal neovascularization. Mechanistically, EYE-502 primarily bound to retinoic acid receptors (RARs) and exerted the anti-angiogenic effects by targeting ECs and pericytes via affecting the activation of Wnt/β-catenin and PDGF/PDGFR/PI3K/Akt signaling. Taken together, this study reports a novel retinoic acid drug, EYE-502, which can exert the anti-angiogenic effects by simultaneous targeting of ECs and pericytes.

Abstract Recycling scrap tires provides an alternative source of fine aggregates for the production of rubberized concrete and this will lead to significant increase in concrete frost resistance, environmental protection, and conservation of natural sand and gravel resources. In this paper, a total of 25 groups of rubberized concrete were produced by adding scrap tire rubber particles of different sizes, contents, and pretreatment methods to replace the fine aggregate, and their compressive strength during freeze–thaw cycles was studied from both the macro- and meso-perspectives. The results indicated that the decrease in concrete strength and weight was notably restricted by the presence of rubber particles during freeze–thaw cycles. The rubber fine aggregate with smaller particle sizes enhanced the concrete frost resistance more significantly, and the F 100 of concrete with rubber particles of 1.0–2.0 mm increased from 76.6 to 86.5% by increasing the rubber content from 0.0 to 5.6%. The effects of rubber fine aggregate on concrete compressive strength during freeze–thaw cycles were quantified. On this basis, a forecast model for rubberized concrete compressive strength in freeze–thaw cycles was proposed, and the effects of the particle size, content, and pretreatment of the rubber particles were considered. The calculated results agreed well with the test results both in this study and the relevant peer studies, indicating that the model can provide a good reference for the design and engineering application of rubberized concrete in frigid environments.

Abstract By the popularization of Internet, and mobile terminals, there are more and more activities that are helpful for rehabilitation training. Among them, software products represented by sports pedometers have attracted much attention. Based on mastering one’s own physical condition, one can carry out effective social activities, such as brisk walking, running, etc., to improve people’s communication, thereby enriching people’s leisure activities, and thus achieving the purpose of rehabilitation. Therefore, this paper proposes the design, and implementation of basic course teaching system for sports rehabilitation based on the Android platform. This paper mainly analyzed the health system of Android platform. Researchers have thoroughly researched Motor Imagery (MI) rehabilitation training, and their algorithm has been analyzed. An experiment on its efficacy was also conducted in the experimental part, along with a system modeling exercise. The final experimental results showed that the success rate of motor imagery direction control in G1 group was 59.88%, 58.89%, and 59.22%, and the G2 group was 64.22%, 63.33%, and 64.11%. The results showed that G2 using feedback information had a significantly higher success rate of action imagery than G1 that did not provide the feedback information under different test modes. Therefore, feedback information in motor fantasy training can improve motor fantasy effect.

Climatic droplet keratopathy (CDK) is a corneal diseases, which is characterized by increased oil-like deposits on the anterior elastic lamina and anterior stromal layer. Severe CDK can even cause blindness, with no specific available treatment. Besides. CDK is poorly understood in terms of its pathogenic mechanisms. Thus, to determine potential biomarkers for CDK, we analyzed the microRNA expression profile in tear samples from CDK patients and investigated their putative roles in the pathogenesis of CDK. Herein, miRNA sequencing and following bioinformatics analysis was performed to explore the roles of their target genes in CDK. A total of 67 differentially expressed miRNAs were identified, of which 25 were upregulated and 42 were downregulated. qPCR verification showed that among the up- and down-regulated miRNAs, expression of five and six, respectively, was most significantly different.The target genes of the differentially expressed miRNAs are involved in the FoxO signaling pathway, tumor necrosis factor (TNF) signaling pathway, and steroid hormone biosynthesis. Protein–protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. In conclusion, the panel of differentially expressed miRNAs identified may have potential utility as early diagnostic biomarkers for CDK. Moreover, the TNF signaling pathway is a new potential target in CDK for the development of treatments.

IntroductionGift-giving is a prevalent practice in daily life, with experiential gifts being identified in studies as having hedonic and interpersonal advantages, often yielding greater recipient satisfaction compared to material gifts. However, the reception of experiential gifts might not always align with expectations, as material gifts are valued for their enduring qualities. Thus, comprehending the contexts favoring material or experiential gift preferences becomes crucial.MethodsExisting research primarily delves into external influences like income and social proximity, while intrinsic factors such as personal sense of power in interpersonal interactions have received limited attention. Guided by the Agentic-communal Model of Power, we conducted three studies to investigate how personal sense of power impact gift preferences.ResultsOur findings demonstrated that gift preferences are contingent upon personal sense of power. Specifically, those possessing a high personal sense of power exhibited a preference for material gifts over experiential ones, whereas individuals with a low personal sense of power favored experiential gifts over material ones. Further analysis revealed that the relationship between personal sense of power and gift preference is mediated by information processing fluency.DiscussionThis study contributes to the field of gift preferences and sheds light on the role of personal sense of power. By incorporating the Agentic-communal Model of Power, we offer novel insights into the dynamics between personal sense of power and gift preferences. These findings hold valuable implications for managerial strategies concerning gift selection and interpersonal interactions.

Abstract Multiple myeloma (MM) is an incurable plasma cell hematological malignancy. Bortezomib has become the primary drug in the treatment of patients with MM. However, its negative effects, especially peripheral neuropathy (PN), affect the patients’ life quality and treatment continuity. However, there are few studies on baseline PN of MM, and little is known of the impact of baseline PN on the prognosis of MM patients. Therefore, we reviewed the clinical data of newly diagnosed MM patients in our center, explored the influencing factors of baseline PN, and evaluated PN’s influence on the prognosis of MM patients undergoing induction therapy with bortezomib. According to the inclusion and exclusion criteria, 155 MM patients were eligible for the retrospective study. The multivariate regression analysis, generalized additive fitting smooth curve, the receiver operating characteristic curve (ROC) and K-M curve were conducted in this study. We found that baseline PN in patients with MM was age-related; MM patients with baseline PN have more severe bortezomib induced PN (BiPN) during the four courses of induction therapy with bortezomib as the primary regimen and worse PN outcome after induction therapy. Additionally, the progression-free survival (PFS) and overall survival (OS) of MM patients with baseline PN were worse than those of the MM patients without baseline PN.

Continuous cropping is the main form of cultivation in Chinese agriculture. The bacterial community plays an important role in maintaining the healthy growth of plants. However, there are few reports on the composition and dynamics of the bacterial community structure under continuous cropping of Lonicera japonica Thunb. High-throughput sequencing was used to monitor the variation in the soil bacterial community structure of different monocropping years of Lonicera japonica Thunb., as well as the correlation between soil characteristics and bacterial community. Meanwhile, antagonistic bacteria for Fusarium oxysporum pathogens were isolated and functionally verified by culture-dependent techniques and pot experiments. Bacterial community diversity and structure changed significantly with the increase in the years of Lonicera japonica Thunb. succession. However, some beneficial bacteria, such as Bacillus and Nitrosospira, were gradually depleted. The complexity of the bacteria co-occurrence networks decreased with increasing years of cropping. FAPROTAX-based functional prediction showed that the abundance of genes related to carbon, nitrogen, sulfur metabolism and chitinlysis were reduced with the extended crop succession. Furthermore, the three Bacillus strains that were strongly antagonistic toward Fusarium oxysporum and the pot experiment demonstrated they significantly promoted Lonicera japonica Thunb. growth. Our research provides theoretical support for the development of microbial fertilizers that are beneficial to plants.

A pulse duration compression technique that combines stimulated Brillouin scattering (SBS) and stimulated Raman scattering (SRS) was presented in this study, achieving an output pulse duration of 48.3 ps. The feasibility of this approach has been experimentally demonstrated. To be specific, a pulse duration of 7.4 ns is compressed to 48.3 ps with an energy of 5.27 mJ, and the energy efficiency of the SRS pulse duration compression system is up to 21.84%. Moreover, this study provides a practical method for reliably generating high-energy short pulses.

Abstract Multiple myeloma (MM) remains an incurable plasma cell cancer characterized by abnormal secretion of monoclonal immunoglobulins. The molecular mechanism that regulates the drug sensitivity of MM cells is being intensively studied. Here, we report an unexpected finding that the protein encoded by neural precursor cell-expressed developmentally downregulated gene 4L (NEDD4L), which is a HECT E3 ligase, binds the 19S proteasome, limiting its proteolytic function and enhancing autophagy. Suppression of NEDD4L expression reduced bortezomib (Bor) sensitivity in vitro and in vivo, mainly through autophagy inhibition mediated by low NEDD4L expression, which was rescued by an autophagy activator. Clinically, elevated expression of NEDD4L is associated with a considerably increased probability of responding to Bor, a prolonged response duration, and improved overall prognosis, supporting both the use of NEDD4L as a biomarker to identify patients most likely to benefit from Bor and the regulation of NEDD4L as a new approach in myeloma therapy.

Objective To explore the performance verification of NAT and its procedures for HBV DNA, HCV RNA and HIV RNA-1 using PCR-fluorescence via Cobas s201 automatic NAT system and supporting MPX V2.0 reagents that applied in the laboratories of blood stations, in order to satisfy ISO 15189 accreditation requirements and ensure the accuracy of NAT results. Methods Samples used in external quality assessment(EQA) of year 2020 were taken to verify the concordance, Performance evaluation panel and sensitivity verification panel of Roche second-generation NAT system were used to verify the sensitivity/ specificity and the lower limit of detection, respectively.And HBV DNA, HCV RNA and HIV RNA-1 quality control products were used to verify the anti-interference ability. Results The concordance rate of 40 EQA, samples was 100%. The sensitivity and specificity of Cobas s201 automatic NAT system and supporting MPX V2.0 reagents in detecting HBV DNA, HCV RNA and HIV RNA-1 were all 100%. The lower detection limit for HBV DNA, HCV RNA and HIV RNA-1 all met the requirements of reagent instructions. The yielding of HBV DNA, HCV RNA and HIV RNA-1 were affected little with hemolysis at 500 mg/dL but interfered seriously as lipemia reached 3 300 mg/dL. Conclusion The concordance rate, sensitivity, specificity and lower detection limit of the Cobas s201 fully-automatic NAT system and MPX V2.0 reagents by PCR-fluorescence method all met the requirements of reagent instructions. The verification of anti-interference ability demonstrated the requirements of ISO 15189 and the needs of blood station laboratories could be satisfied, and the detection methods and procedures can ensure the accuracy of NAT results.

BackgroundMultiple myeloma is genetically heterogeneous, and chromosome abnormalities play a pivotal role in prognosis. A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities; however, its relationship with overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma is still unclear. We aim to clarify the impact of +1q on the clinical characteristics and survival outcomes of patients treated with bortezomib-based combination regimes.Materials and methodsWe retrospectively analyzed 258 patients first diagnosed with myeloma who underwent bortezomib-based therapy at the bone marrow transplantation department of a multiple myeloma treatment center in the first affiliated hospital of Zhejiang University, China.ResultsWe identified 258 newly diagnosed patients with multiple myeloma in our department from July 2013 to September 2018. We observed that 127 (49.2%) of the patients acquired +1q at diagnosis, and +1q strongly correlated with the occurrence of del(13q) and IgH rearrangement (P < 0.001). In the patients with +1q, the PFS was 22.2 months (95% CI 15.8–28.5 months), and the three-year and five-year PFS was 35.1% and 15.3%, respectively. Univariate analysis revealed that albumin, lactate dehydrogenase (LDH), and the percentage of plasma cells significantly affected PFS. Multivariate analysis showed that LDH and the percentage of plasma cells significantly affected PFS in the +1q patients. In terms of OS, the median OS for the +1q patients was 47.4 months (95% CI 34.7–59.5), while the OS of the non-+1q patients was not reached (P = 0.048). The univariate and multivariate analyses revealed that age, platelet count, and extramedullary lesions were significant adverse factors for OS in the +1q patients. There were no statistical differences between PFS and OS when there were other chromosomal abnormalities, but there was a decreased tendency in PFS. LDH and +1q also had a synergistic adverse effect on survival.Conclusion+1q is associated with a higher tumor burden and correlated with the occurrence of del(13q) and IgH rearrangement at diagnosis. In the era of novel agents, +1q still significantly affects PFS and OS.

Abstract Background Investigation of the prevalence of climatic droplet keratopathy (CDK) in Tacheng, Xinjiang, China. Methods A total of 1030 participants, in their 40s or older, from the Kazakh ethnic group in Tacheng, were randomly sampled by stratification method. Ophthalmic examinations and surveys were carried out on these participants. Factors associated with CDK were analyzed with logistic regression models. Results CDK was found in 66 (6.4%; 95% confidence interval [CI]: 4.9–7.9%) Kazakh individuals. After multiple regression model analysis, it demonstrated that age (

BackgroundMatrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) have documented roles in the inflammatory injury cascade of neurovascular units following ischemic brain injury. However, their dynamic changes and predictive values after acute ischemic stroke (AIS) have not been well elucidated.ObjectiveTo investigate the temporal profiles of serum MMP-9 and BDNF concentrations and their relationship with the prognosis in patients with AIS.MethodsMMP-9 and BDNF levels were measured in 42 AIS patients in prospectively collected blood samples, which were taken on the first day (Day 1), the second day (Day 2), and the fifth day (Day 5) after admission. Healthy subjects (n = 40) were used as controls. The AIS patients were divided into groups of good functional prognosis (n = 24) and poor prognosis (n = 18) according to their modified Rankin Scale score at 3 months. Longitudinal analysis of MMP-9 and BDNF and their association with neurological prognosis was performed using repeated measurement ANOVA.ResultsAt baseline (Day 1), the levels of serum MMP-9 and BDNF were significantly higher in the AIS group than in the normal control group (P < 0.01). Repeated measurement ANOVA showed a significant main effect and interaction of MMP-9 between good prognosis and the poor group (P < 0.05). Further simple-effect analysis showed that the MMP-9 level was significantly increased in the poor prognosis group compared with the good prognosis group at T5 (P < 0.05). There were no significant time-dependent or the interaction effect (all P > 0.05), but a main effect (P < 0.05) for BDNF. Compared with the poor prognosis group, the simple-effect results indicated that the BDNF level of the good prognosis group was lower at Day 1, while the same was reversed for expression at Day 5 (P < 0.05).ConclusionMMP-9 and BDNF are closely related to the prognosis of patients with AIS in a time-dependent manner. The dynamic changes of the two biomarkers are superior to baseline levels in predicting the prognosis of AIS patients. A sustained decrease in MMP-9 and an increase in BDNF levels in AIS patients after several days of treatment implied a favourable prognosis.

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion < 0.0001, pfracture < 0.0001). The violin plot showed that MM patients with higher serum IL-17A levels had more severe bone lesions and higher fracture incidence than those with lower serum IL-17A levels. A total of 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A levels were independently related to the best inductive therapeutic efficacy (fully adjusted model, p = 0.037), and the relationship was especially obvious in the light chain group (fully adjusted model, p = 0.009) and IgA group (fully adjusted model, p = 0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (p = 0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (area under the curve (AUC) = 0.717, p = 0.0327). A total of 148 MM patients were observed in the longitudinal study of the relationship between serum IL-17A and progression-free survival/overall survival (PFS/OS). The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (p = 0.015) and OS (p = 0.0076) compared to those with low serum IL-17A. In the IgA type subgroup, the higher IL-17A level was related to worse OS (p = 0.0061).ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.

Oscillations caused by the interaction between voltage source converters (VSCs) and weak grids are vital threats to the stability of power systems. Determining the appropriate parameters for the control of VSCs is essential to prevent the occurrence of oscillations in advance. To achieve this goal, a quantitative evaluation method of system stability for VSCs is proposed in this article to specify the stability boundary of control parameters. Then, an active damping controller for current control and a parameter optimization method for the phase-locked loop (PLL) is proposed, and the related parameters are designed based on the guidance of the proposed evaluation method. With planting the parameters optimization in the control of VSC, the stability boundary of control parameters of VSC is extended, so that the stability of VSC can be significantly improved. Finally, simulations are presented to verify the effectiveness of the theoretical analysis.

Abstract The ultra‐low‐frequency oscillation (ULFO) problem has reappeared in China recently. Although the hydraulic generator is supposed to have a strong connection to this problem, the conditions for ULFO appearance and detailed reasons are not clear yet. In order to clarify the occurrence mechanism of ULFO, this paper studies each important part of hydraulic generator system, including the governor, exciter and power system stabiliser (PSS). The weak connection is confirmed to have an important impact on the occurrence of the ULFO. Nevertheless, by studying each device's contribution to ULFO through the complex torque coefficient method, it is shown that the negative damping effect of the hydraulic governor will cause the instability in the ultra‐low‐frequency band, while the exciter and the PSS have little influence on ULFO. Additionally, the proportional–integral parameters of the hydraulic governor system are also studied to clarify their influence on ULFO based on the complex torque coefficient method. Based on the above analysis, two damping methods for ULFO suppression are finally proposed. To verify theory and damping methods, the simulations are implemented in PSCAD and PSASP software.

The chestnuts genus (Castanea spp.) is comprised of economically important trees native to the Northern hemisphere that are used as food and hardwood timber. Here, a very efficient method for micropropagation of European × Japanese chestnut hybrids (Castanea sativa × C. crenata) is described. Woody Plant Medium was used as the basal medium. In vitro shoots of four rootstock cultivars were micropropagated without shoot-tip necrosis on multiplication medium containing 5.7 or 11.4 µmol·L−1 zeatin riboside, and were rooted on rooting medium containing 2.46 µmol·L−1 indolebutyric acid. Monthly shoot multiplication rates for each cultivar were 2–5 folds. In vitro rooting percentages for four cultivars were 87% for ‘Maraval’, 67% for ‘Marigoule’, 93% for ‘Marsol’, and 97% for ‘Précoce Migoule’. Within a 5 week period, 80%–95% of rooted shoots were successfully acclimated under high humidity conditions after they were planted in either soil or rockwool.

Abstract Plant roots and soil prokaryotes primarily interact with each other in the rhizosphere. Changes in the rhizosphere prokaryotic structure are influenced by several factors. In this study, the community structure of the Potentilla anserina L. rhizosphere prokaryotes was identified and evaluated by high-throughput sequencing technology in different continuous cropping fields and developmental stages of the plant. In total, 2 archaeal (Euryarchaeota and Thaumarchaeota) and 26 bacterial phyla were identified in the P. anserina rhizosphere. The bacterial community was mainly composed of Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Gemmatimonadetes, Planctomycetes, Proteobacteria, and Verrucomicrobia. Moreover, the prokaryotic community structure of the rhizosphere varied significantly during plant development. Our results provide new insights into the dynamics of the P. anserina rhizosphere prokaryotic community and may provide useful information for enhancing the growth and development of P. anserina through artificial control of the soil prokaryotes.

BackgroundType I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis.ObjectiveThis study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia.MethodsWe conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium.ResultsProband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 ± 9.46% (p

BackgroundThe relationship between obesity and diabetic retinopathy (DR) remains controversial. The aim of this study was to assess the association of generalized obesity [assessed by body mass index (BMI)] and abdominal obesity [assessed by waist to hip ratio (WHR)] with incident DR, and vision-threatening DR (VTDR), and DR progression among Chinese adults with type 2 diabetic mellitus (T2DM).MethodThis prospective cohort study was conducted at the Zhongshan Ophthalmic Center, from November 2017 to December 2020. DR was assessed based on the 7-filed fundus photographs using the modified Airlie House Classification. Multivariable logistic regression models were used to evaluate the associations of BMI and WHR with the development and progression of DR after adjusting for age, sex, traditional risk factors, and mutually for BMI and WHR.ResultsAmong the 1,370 eligible participants, 1,195 (87.2%) had no sign of any DR and 175 (12.8%) had DR at baseline examination. During the 2 years follow-up visit, 342 (28.6%) participants had incident DR, 11 (0.8%) participants developed VTDR, 15 (8.6%) demonstrated DR progression. After adjusting for confounders, the BMI was negatively associated with incident DR [relative risk (RR) =0.31; 95% confidence interval (CI), 0.26–0.38; P < 0.001] and incident VTDR (RR = 0.22; 95%CI, 0.11–0.43; P < 0.001), while WHR was positively associated with incident DR (RR = 1.47; 95% CI, 1.27–1.71; P < 0.001). BMI and WHR level were not significantly associated with 2-year DR progression in multivariate models (all P > 0.05).ConclusionsThis study provides longitudinal evidence that generalized obesity confer a protective effect on DR, while abdominal obesity increased the risk of DR onset in Chinese patients, indicating that abdominal obesity is a more clinically relevant risk marker of DR than generalized obesity.

Abstract Background To investigate the distribution of corneal astigmatism, aberration, and biometric parameters in Chinese congenital cataract (CC) /developmental cataract patients before cataract surgery. Methods We evaluated eyes of CC /developmental cataract patients scheduled for cataract surgery from January 2016 to September 2019. Astigmatism, aberrations, and biometric parameters were measured with the Pentacam Scheimpflug imaging device (Pentacam HR, Oculus). Cataract was diagnosed and classified by slit-lamp examination after full mydriasis. Results We evaluated 538 eyes in 356 patients. The mean values of anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), and total corneal astigmatism (TCA) were determined as 1.98 ± 1.06 D (range 0.0‒4.8 D), 0.49 ± 0.26 D (range 0.0‒1.9 D), and 2.09 ± 1.19 D (range 0.2‒8.8 D), respectively. ACA and TCA ≥ 1.25 D was present in 379 eyes (70.3%) and 392 eyes (72.8%), respectively. PCA between 0.25 D and 0.75 D was found in 380 eyes (70.6%). There was a statistically significant positive linear correlation between lower-order aberrations root mean square values (LOA RMS) and corneal astigmatism (CA). Furthermore, in terms of distribution of central cornea thickness, anterior chamber depth, ACA, PCA, and TCA in different types of cataracts, ACA was highest in patients with zonular cataracts. Finally, we found anterior corneal measurements may overestimate WTR astigmatism, underestimate ATR astigmatism, and underestimate oblique astigmatism, respectively. Conclusions Most CC /developmental cataract patients had moderate to high astigmatism and ACA accounted for the largest proportion in the zonular group. This can provide a basis for planning of CC/developmental cataract surgery by ophthalmologists in clinical practice.

Uveitis is a severe ocular inflammatory disease that affects the uvea and frequently results in visual impairment, even irreversible blindness. The current treatments for uveitis have exhibited adverse side effects. To find novel targets of this disease, we perform comparative transcriptome analysis using normal (n = 4) and experimental autoimmune uveitis (EAU) (n = 4) rat iris samples. We mainly focus on the expression profiles of mRNAs and long non-coding RNAs, and identify NOD-like receptor signaling pathway as the one that plays a key role in the pathological changes of the EAU irises. Our work demonstrates that the EAU iris transcriptome can be mined to uncover novel targetable pathways for uveitis. The molecules in NOD-like receptor signaling pathway could be novel therapeutic targets for autoimmune uveitis.

ObjectiveTo explore the efficacy and safety of intermittent, oral famciclovir prophylaxis for bortezomib-induced herpes zoster in multiple myeloma patients.MethodWe retrospectively analyzed the incidence of bortezomib treatment-related varicella-zoster virus reactivation in 719 newly-diagnosed multiple myeloma patients receiving intermittent oral famciclovir prophylaxis, continuous oral acyclovir prophylaxis or no prophylaxis. The definition of intermittent oral famciclovir prophylaxis was oral famciclovir at a dose of 250mg twice daily for 9 days after finishing the last dose of bortezomib therapy every cycle. Age, gender, stage per the International Staging System, type of M protein, baseline of absolute lymphocyte count, absolute neutrophil count, and absolute monocyte count were analyzed to find the potential factors that could predispose to herpes zoster infections.ResultsVaricella-zoster virus infection occurred in 96 patients (13.4%) during bortezomib treatment. The incidence of herpes zoster was significantly higher in the non-prophylaxis group compared with the prophylaxis group (22.9% vs 8.2% P

The seeds of Chinese horse chestnut are used as a source of starch and escin, whereas the potential use of whole plant has been ignored. The astringency and bitterness of tea produced from the leaves and flowers were found to be significantly better than those of green tea, suggesting that the enriched flavonoids maybe sensory determinates. During 47 flavonoids identified in leaves and flowers, seven flavonol glycosides in the top 10 including astragalin and isoquercitrin were significantly higher content in flowers than in leaves. The crude proteins of flowers could catalyze flavonol glucosides' formation, in which three glycosyltransferases contributed to the flavonol glucosylation were screened out by multi-dimensional integration of transcriptome, evolutionary analyses, recombinant enzymatic analysis and molecular docking. The deep exploration for flavonol profile and glycosylation provides theoretical and experimental basis for utilization of flowers and leaves of Aesculus chinensis as additives and dietary supplements.

Gambogic acid (GA) refers to a xanthonoid that exhibits significant antitumor activity due to its poor solubility and low bioavailability. For this reason, its shortcoming should be overcome using novel approaches to improve its practical effectiveness. In this study, with the use of ion exchange method, GA was encapsulated in layered double hydroxide (LDH). In the GA-LDH nanohybrid, GA was distributed and stabilized in the interlamellar region of LDH through intermolecular interactions. GA-LDH was further modified by liposome (LS) through ethanol injection method. The drug encapsulation efficiency of GA-LDH/LS was obtained as 56.28%. The chemical structures and physicochemical properties exhibited by GA-LDH/LS were characterized and confirmed using different instruments, and drug release showed that GA-LDH/LS had significantly sustained release due to the combined effect of the matrix LDH and the phospholipid bilayer. Furthermore, GA-LDH/LS displayed lower hemolysis percentage than GA-LDH during the hemolysis test. This study suggested that GA-LDH/LS nanocomposite could be a promising antitumor drug delivery system due to its outstanding performance in biomedical research.

Abstract Red blood cells (RBCs) and platelets derived from stem cells are possible solutions to the increasing demand for blood transfusion. Based on the availability of stem cells, their relatively defined differentiation mechanisms, and the massive exploration of induction systems, the generation of RBCs or platelets in vitro from cord blood hematopoietic stem/progenitor cells (CB‐HSPCs) has potential for clinical applications. However, information on the clinical translation of stem cell‐derived RBCs and platelets in the literature and at the ClinicalTrials.gov website is very limited. The only clinical trial on cultured RBCs, which aimed to assess the lifespan of RBCs cultured in vivo, was reported by Luc Douay and colleagues. Of note, the cultured RBCs they used were derived from autologous peripheral blood HSPCs, and no cultured platelets have been applied clinically to date. However, CB‐HSPC‐derived megakaryocytes, platelet precursors, have been used in the treatment of thrombocytopenia. A successful phase I trial was reported, followed by phase II and III clinical trials conducted in China. In this review, the gap between the many basic studies and limited clinical trials on stem cell‐derived RBCs and platelets is summarized. The possible reasons and solutions for this gap are discussed. Further technological improvements for blood cell expansion and maturation ex vivo and the establishment of biological standards for stem cell derivatives might help to facilitate the therapeutic applications of cultured RBCs and platelets derived from CB‐HSPCs in the near future.

The retinal layer segmentation technique of optical coherence tomography (OCT) data is essential for the diagnosis of ophthalmic and systemic diseases. To achieve fast and accurate retinal layer segmentation, a new medical image segmentation method (wave algorithm) is proposed based on the mathematical model of the fluid potential energy equation in fluid mechanics. A change in the gray value in the image is converted into a change in the potential energy in the ideal fluid (wave), thereby transforming the image segmentation problem into a problem that solves the potential energy based on the fluid potential energy equation. In the process of solving the fluid energy, it is necessary to constrain the potential energy according to the prior knowledge of the medical image. The method consists of two parts: the wave potential energy equation and the potential energy correction equation. When the method is applied to the retinal layer segmentation of an OCT image, the method first detects the boundary area of the retinal layer according to the wave potential energy equation and then uses the potential energy correction equation to accurately extract the boundary line from the boundary area. The proposed method is tested on publicly available datasets. The results show that compared with other advanced segmentation methods, the method achieved slightly superior segmentation accuracy and speed. When the mean unsigned positioning error of the retinal layer segmentation is less than 1.5 pixels, the method can quickly segment the retinal layer at a speed of 1.19 per B-scan/seconds.

Abstract Background This study was conducted to evaluate the impact of a comprehensive community intervention on cognition and inoculation behaviors of diabetic patients immunized with influenza vaccine. Methods A total of 1538 diabetic patients aged 35 years and above for outpatient visits and follow-up treatments were selected from six community health service centers (three for the experimental group, and the other three for the control group) in Chaoyang District, Beijing. Comprehensive interventions applied to the experimental group include patient intervention and community climate interventions. We compared the total awareness of influenza vaccine knowledge and influenza vaccination rates between the two groups before and after the intervention. Results Before the intervention, the total awareness rate of influenza vaccine in the experimental group and the control group was similar (50.6 and 50.2%, respectively. P = 0.171). After the intervention, the awareness rate of influenza vaccine in the experimental group and the control group increased. The amplitude of the increase was similar (70.3 and 70.1%, respectively. P = 0.822,). Before the intervention, there was no significant difference in the influenza vaccination rate between the experimental group and the control group (29.0 and 26.8%, respectively. P = 0.334). After the intervention, the vaccination rate of the experimental group was higher than that of the control group. The difference was statistically significant (The vaccination rate 45.8 and 27.4% for the experimental group and the control group, respectively. P

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

Objective: Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients.Methods: The list of immunity-associated genes was retrieved from ImmPort database. The gene and clinical information of CSCC patients were obtained from The Cancer Genome Atlas (TCGA) website. The immune gene signature for predicting overall survival (OS) of CSCC patients was constructed using the univariate Cox-regression analysis, random survival forests, and multivariate Cox-regression analysis. This signature was externally validated in GSE44001 cohort from Gene Expression Omnibus (GEO). Then, based on the established signature and the TCGA cohort with the corresponding clinical information, a nomogram was constructed and evaluated via Cox regression analysis, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots and decision curve analyses (DCAs).Results: A 5-immune-gene prognostic signature for CSCC was established. Low expression of ICOS, ISG20 and high expression of ANGPTL4, SBDS, LTBR were risk factors for CSCC prognosis indicating poor OS. Based on this signature, the OS was significantly worse in high-risk group than in low-risk group (p-value < 0.001), the area under curves (AUCs) for 1-, 3-, 5-years OS were, respectively, 0.784, 0.727, and 0.715. A nomogram incorporating the risk score of signature and the clinical stage was constructed. The C-index of this nomogram was 0.76. AUC values were 0.811, 0.717, and 0.712 for 1-, 3-, 5-years OS. The nomogram showed good calibration and gained more net benefits than the 5-immune-gene signature and the clinical stage.Conclusion: The 5-immune-gene signature may serve as a novel, independent predictor for prognosis in patients with CSCC. The nomogram incorporating the signature risk score and clinical stage improved the predictive performance than the signature and clinical stage alone for predicting 1-year OS.

IntroductionWe analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients.MethodsA total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed.ResultsThe maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2–3, DS 2–3, and RISS 2–3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292).ConclusionPIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.

Introduction: Personal lifestyle and air pollution are potential risk factors for major non-communicable diseases (NCDs). However, these risk factors have experienced dramatic changes in the Beijing–Tianjin–Hebei (BTH) region in recent years, and few cohorts have focused on identifying risk factors for major NCDs in this specific region. The current study is a large, prospective, long-term, population-based cohort study that investigated environmental and genetic determinants of NCDs in BTH areas. The results of this study may provide scientific support for efforts to develop health recommendations for personalized prevention.Methods: About 36,000 participants 18 years or older would be obtained by multistage, stratified cluster sampling from five cities for the baseline assessment. Participants underwent seven examinations primarily targeting respiratory and circulatory system function and filled out questionnaires regarding lifestyle behavior, pollutant exposure, medical and family history, medication history, and psychological factors. Biochemistry indicators and inflammation markers were tested, and a biobank was established. Participants will be followed up every 2 years. Genetic determinants of NCDs will be demonstrated by using multiomics, and risk prediction models will be constructed using machine learning methods based on a multitude of environmental exposure, examination data, biomarkers, and psychosocial and behavioral assessments. Significant spatial and temporal differentiation is well-suited to demonstrating the health determinants of NCDs in the BTH region, which may facilitate public health strategies with respect to disease prevention and survivorship-related aspects.

Some subtypes of acute myeloid leukemia (AML) share morphologic, immunophenotypic, and clinical features of acute promyelocytic leukemia (APL), but lack a PML–RARA (promyelocytic leukemia–retinoic acid receptor alpha) fusion gene. Instead, they have the retinoic acid receptor beta (RARB) or retinoic acid receptor gamma (RARG) rearranged. Almost all of these AML subtypes exhibit resistance to all-trans retinoic acid (ATRA); undoubtedly, the prognosis is poor. Here, we present an AML patient resembling APL with a novel cleavage and polyadenylation specific factor 6 ( CPSF6 ) –RARG fusion, showing resistance to ATRA and poor response to chemotherapy with homoharringtonine and cytarabine. Simultaneously, the patient also had extramedullary infiltration.

Background/Aims. To investigate the long-term efficacy and rotational stability of toric intraocular lenses (IOLs) implanted for the correction of moderate-to-high corneal astigmatism. Methods. A total of 57 cataract patients (57 eyes) with regular corneal astigmatism (≥2.57 D) were enrolled in this retrospective cohort study. Phacoemulsification with toric IOL implantation was performed for all patients. The uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were recorded before and one year after surgery, and statistical analysis of preoperative corneal astigmatism, postoperative residual astigmatism, aberrations, IOL rotation, and related factors was performed to evaluate the efficacy, safety, and stability of toric IOLs in correcting moderate-to-high corneal astigmatism. Results. One year after surgery, visual acuity was significantly improved compared with that before surgery (preoperative log MAR 0.87 ± 0.34 vs. postoperative log MAR 0.31 ± 0.26, p

Background: Improve the treatment quality might affect patients’ efficacy and survival.Methods: Five hundred thirty multiple myeloma patients treated in four hematological centers in China from February 2006 to August 2018 were enrolled. General characteristics, treatment regimens and cycles, efficacy, survival and adverse events of the patients treated before and after August 2013 (later refer to as the before-2013 and after-2013 group) were analyzed and compared.Results: The results suggested that patients who received optimized treatment regimen and route of administration completed more cycles of treatment in the after-2013 group. Although the overall response rate was similar between the two groups (88.6 vs. 90.5%), patients in the after-2013 group had higher complete remission rate (39.1 vs. 28.6%) and better progression-free survival. Subgroup analysis suggested that patients aged 65 years and older, with non-high-risk D-S, ISS, and R-ISS stages, had a significant benefit in progression-free survival.Conclusion: Therefore, in clinical practice in China, by reducing the economic burden brought by the treatment on patients and optimizing the treatment regimen, more patients can be treated with better regimens in a prolonged duration to achieve better efficacy and survival, especially in elderly and non-high-risk patients.

Background: Evidence regarding the effects of long-term and high-level ambient air pollution exposure on cardiac conduction systems remains sparse. Objectives: To investigate the associations of long-term exposure to air pollution and cardiac conduction abnormalities in Chinese adults and explore the susceptibility characteristics. Methods: In 2017, a total of 27,047 participants aged 18–80 years were recruited from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH). The three year (2014–2016) average pollutant concentrations were assessed by a spatial statistical model for PM2.5 and air monitoring stations for PM10, SO2, NO2, O3 and CO. Residential proximity to a roadway was calculated by neighborhood analysis. Associations were estimated by two-level generalized linear mixed models. Stratified analyses related to demographic characteristics, health behaviors, and cardiometabolic risk factors were performed. Two-pollutant models were used to evaluate the possible role of single pollutants. Results: We detected significant associations of long-term air pollutant exposure with increased heart rate (HR), QRS and QTc, such that an interquartile range increase in PM2.5 was associated with 3.63% (95% CI: 3.07%, 4.19%), 1.21% (95% CI: 0.83%, 1.60%), and 0.13% (95% CI: 0.07%, 0.18%) changes in HR, QRS and QTc, respectively. Compared to the other pollutants, the estimates of PM2.5 remained the most stable across all two-pollutant models. Similarly, significant associations were observed between living closer to a major roadway and higher HR, QRS and QTc. Stratified analyses showed generally greater association estimates in older people, males, smokers, alcohol drinkers, and those with obesity, hypertension and diabetes. Conclusions: Long-term exposure to ambient air pollution was associated with cardiac conduction abnormalities in Chinese adults, especially in older people, males, smokers, alcohol drinkers, and those with cardiometabolic risk factors. PM2.5 may be the most stable pollutant to reflect the associations.

Renewable energy is widely used as a clean energy in the world, yet the intermittent of the power generation from renewable energy power plants, resulting in poor quality of power supply. However, the hybrid energy system and some energy storage devices can be installed to mitigate the power fluctuation, to achieve power smoothing and maximize the profit, a double-objective optimization model of hybrid system integrated with micro-hydro power (MHP), photovoltaic (PV), and pumped hydro storage (PHS) is established in this study. The day-ahead optimized operation strategy of the PHS based-on hour-level data of seven days is obtained, which aims to maximize the similarity value (SIM) between the power generation curve and load profile, and the economic revenue (ER) of the PHS. Optimized schedule is obtained by means of chance-constrained programming (CCP) and modified multi-objective particle swarm optimization (MOPSO). The performance of the model is evaluated by using the meteorological, the historical MHP power generation and the load data obtained in Xiaojin County, Sichuan province, China. The simulation results reveal that the best trade-off value between SIM and ER can be obtained on the Pareto front with comprehensive consideration of the system operation strategy and target. Furthermore, the generation/load similarity can be increased 7.89% under the participating of the PHS.