Development of a Novel Multidimensional Measure of Aging to Predict Mortality and Morbidity in the Prospective MJ Cohort.

BACKGROUND: Although biological aging has been proposed as a more accurate measure of aging, few biological aging measures have been developed for Asians, especially for young adults. METHODS: A total of 521 656 participants were enrolled in the MJ cohort (1996-2011) and were followed until death, loss-to-follow-up, or December 31, 2011, whichever came first. We selected 14 clinical biomarkers, including chronological age, using a random forest algorithm, and developed a multidimensional aging measure (MDAge). Model performance was assessed by area under the curve (AUC) and internal calibration. We evaluated the associations of MDAge and residuals from regressing MDAge on chronological age (MDAgeAccel) with mortality and morbidity, and assessed the robustness of our findings. RESULTS: MDAge achieved an excellent AUC of 0.892 in predicting all-cause mortality (95% confidence interval [CI]: 0.889-0.894). Participants with higher MDAge at baseline were at a higher risk of death (per 5 years, hazard ration [HR] = 1.671, 95% CI: 1.662-1.680), and the association remained after controlling for other variables and in different subgroups. Furthermore, participants with higher MDAgeAccel were associated with shortened life expectancy. For instance, compared to men who were biologically younger (MDAgeAccel ≤ 0) at baseline, men in the highest tertiles of MDAgeAccel had shortened life expectancy by 17.23 years. In addition, higher MDAgeAccel was associated with having chronic disease either cross-sectionally (per 1-standard deviation [SD], odds ratio [OR] = 1.564, 95% CI: 1.552-1.575) or longitudinally (per 1-SD, OR = 1.218, 95% CI: 1.199-1.238). CONCLUSION: MDAge accurately predicted mortality and morbidity, which has great potential in the early identification of individuals at higher risk and therefore promoting early intervention.

Temporal changes in serum uric acid and risk for metabolic syndrome: a longitudinal cohort study.

BACKGROUND: Studies suggested elevated serum uric acid (SUA) levels are associated with metabolic syndrome (MetS). However, it remains unclear whether baseline SUA and temporal changes predict MetS. The study aimed to investigate the association of baseline SUA and its temporal longitudinal changes with subsequent risk of MetS. METHODS: We conducted a retrospective longitudinal cohort study among 44,176 healthy participants aged 18 years and older without MetS at enrollment. The baseline levels and longitudinal changes of SUA were categorized by gender-specific quintiles. Participants were followed to identify newly developed MetS. We employed Cox model to investigate the relationship between SUA and MetS in men and women separately. RESULTS: During a median follow-up of 2.4 years, 5461 (12.36%) participants developed MetS. After adjustment of demographic, major clinical factors, a higher level of baseline SUA was associated with a significant higher risk of MetS. The corresponding HRs (95% CIs) comparing participants at extreme quintiles were 2.59 (2.32, 2.88) in men and 2.87 (2.41, 3.43) in women. Larger longitudinal absolute increase in SUA was also related to an increases risk of MetS (top vs bottom quintile, 1.70 [1.53, 1.89] in men and 1.94 [1.65, 2.28] in women), regardless the level of baseline SUA. Similarly, the HRs about SUA longitudinal percentage changes were 1.74 (1.56, 1.94) in men and 2.01 (1.69, 2.39) in women, respectively. Moreover, we observed the highest risk of MetS among participants with both higher baseline SUA and larger longitudinal increase in SUA. CONCLUSION: Higher baseline SUA and larger temporal increase in SUA independently predicted risk of MetS, highlighting the importance of longitudinal SUA monitoring and management for primary prevention of MetS in the general population.

Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study.

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

Deep Fuzzy Min-Max Neural Network: Analysis and Design.

Fuzzy min-max neural network (FMNN) is one kind of three-layer models based on hyperboxes that are constructed in a sequential way. Such a sequential mechanism inevitably leads to the input order and overlap region problem. In this study, we propose a deep FMNN (DFMNN) based on initialization and optimization operation to overcome these limitations. Initialization operation that can solve the input order problem is to design hyperboxes in a simultaneous way, and side parameters have been proposed to control the size of hyperboxes. Optimization operation that can eliminate overlap region problem is realized by means of deep layers, where the number of layers is immediately determined when the overlap among hyperboxes is eliminated. In the optimization process, each layer consists of three sections, namely, the partition section, combination section, and union section. The partition section aims to divide the hyperboxes into a nonoverlapping hyperbox set and an overlapping hyperbox set. The combination section eliminates the overlap problem of overlapping hyperbox set. The union section obtains the optimized hyperbox set in the current layer. DFMNN is evaluated based on a series of benchmark datasets. A comparative analysis illustrates that the proposed DFMNN model outperforms several models previously reported in the literature.

Effect of acupoint therapies on chemotherapy-induced nausea and vomiting: A systematic review protocol.

BACKGROUND: Patients suffering from chemotherapy-induced nausea and vomiting (CINV) might have negative adherence of treatment. Acupoint therapies, including acupuncture, acupressure, acupoints injection, massage, and moxibustion, are safe medical procedures with minimal side effects for CINV, but studies about overall safety and effectiveness of acupoint therapies have not been scientifically and methodically evaluated in recent years. Evaluating the overall safety and effectiveness of acupoint therapies in patients with CINV is the purpose of this review. METHODS AND ANALYSIS: Relevant randomized controlled trials (RCTSs) are being searched in the following electronic databases: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). We will also attempt to obtain the unpublished academic data by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of the acupoint therapies for CINV patients will be searched in the databases from inception to July 2019. The primary outcomes are defined as severity, duration and frequency of nausea or vomiting, or both. The secondary outcomes are defined as any adverse events and quality of life. Performing the meta-analysis by using RevMan version 5 software. Mean difference (MD) or standardized mean difference (SMD) will express the continuous variables, while relative risk (RR) will express the categorical variables. RESULTS: The results of this review will provide a high-quality synthesis to evaluate the effectiveness and safety of acupoint therapies for CINV. CONCLUSION: This review will provide evidence to estimate whether acupoint therapies are effective interventions for CINV. DISSEMINATION: Evidence whether acupoint therapies are effective interventions for CINV will be provided by this systematic review. This knowledge will recommend better acupoint therapies and selections of acupoints which might be helpful in treating CINV. The findings of this systematic review will be disseminated via various forms of presentation and publication of the data in a journal or electronic databases. PROSPERO REGISTRATION NUMBER: CRD42019125538.

Arabidopsis RPG1 is important for primexine deposition and functions redundantly with RPG2 for plant fertility at the late reproductive stage.

Arabidopsis Ruptured Pollen Grain-1 (RPG1/Sweet8) is a member of the MtN3/saliva protein family that functions as a sugar transporter. The rpg1 mutant shows defective exine pattern formation. In this study, transmission electron microscopy (TEM) observations showed that much less primexine was deposited in rpg1 tetrads. Furthermore, microspore membrane undulation was abnormal, and sporopollenin accumulation was also defective. This suggests that a reduced primexine deposition in rpg1 leads to abnormal membrane undulation that affects exine pattern formation. Chemical staining revealed thinning of the callose wall of rpg1, as well as significantly reduced expression of Callose synthase-5 (CalS5) in rpg1. The fertility of the rpg1 mutant could be partly restored at late reproductive stages, potentially complemented in part by RPG2, another member of the MtN3/saliva family, which is expressed in the anther during microsporogenesis. The double mutant, rpg1rpg2, was almost sterile and was not restored during late reproduction. These results suggest that RPG1 and RPG2 are involved in primexine deposition and therefore pollen wall pattern formation.

AUXIN RESPONSE FACTOR17 is essential for pollen wall pattern formation in Arabidopsis.

In angiosperms, pollen wall pattern formation is determined by primexine deposition on the microspores. Here, we show that AUXIN RESPONSE FACTOR17 (ARF17) is essential for primexine formation and pollen development in Arabidopsis (Arabidopsis thaliana). The arf17 mutant exhibited a male-sterile phenotype with normal vegetative growth. ARF17 was expressed in microsporocytes and microgametophytes from meiosis to the bicellular microspore stage. Transmission electron microscopy analysis showed that primexine was absent in the arf17 mutant, which leads to pollen wall-patterning defects and pollen degradation. Callose deposition was also significantly reduced in the arf17 mutant, and the expression of CALLOSE SYNTHASE5 (CalS5), the major gene for callose biosynthesis, was approximately 10% that of the wild type. Chromatin immunoprecipitation and electrophoretic mobility shift assays showed that ARF17 can directly bind to the CalS5 promoter. As indicated by the expression of DR5-driven green fluorescent protein, which is an synthetic auxin response reporter, auxin signaling appeared to be specifically impaired in arf17 anthers. Taken together, our results suggest that ARF17 is essential for pollen wall patterning in Arabidopsis by modulating primexine formation at least partially through direct regulation of CalS5 gene expression.

CYCLIN-DEPENDENT KINASE G1 is associated with the spliceosome to regulate CALLOSE SYNTHASE5 splicing and pollen wall formation in Arabidopsis.

Arabidopsis thaliana CYCLIN-DEPEDENT KINASE G1 (CDKG1) belongs to the family of cyclin-dependent protein kinases that were originally characterized as cell cycle regulators in eukaryotes. Here, we report that CDKG1 regulates pre-mRNA splicing of CALLOSE SYNTHASE5 (CalS5) and, therefore, pollen wall formation. The knockout mutant cdkg1 exhibits reduced male fertility with impaired callose synthesis and abnormal pollen wall formation. The sixth intron in CalS5 pre-mRNA, a rare type of intron with a GC 5' splice site, is abnormally spliced in cdkg1. RNA immunoprecipitation analysis suggests that CDKG1 is associated with this intron. CDKG1 contains N-terminal Ser/Arg (RS) motifs and interacts with splicing factor Arginine/Serine-Rich Zinc Knuckle-Containing Protein33 (RSZ33) through its RS region to regulate proper splicing. CDKG1 and RS-containing Zinc Finger Protein22 (SRZ22), a splicing factor interacting with RSZ33 and U1 small nuclear ribonucleoprotein particle (snRNP) component U1-70k, colocalize in nuclear speckles and reside in the same complex. We propose that CDKG1 is recruited to U1 snRNP through RSZ33 to facilitate the splicing of the sixth intron of CalS5.