Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.

Peking Union Medical College Hospital, as one of the most stressful medical institutions in China, is facing the problem of emergency department overcrowding. In order to effectively alleviate the emergency overcrowding, improve the medical quality and patients′ medical experience, the hospital firmly grasped the two incremental links of " throughput" and " output" factors, established a multidisciplinary and multi-department cooperation team, constructed a close medical alliance cooperation mode, and innovated and explored a harmonious emergency overcrowding relief mode with the goal of unblocking the " exit" of patients. The practice showed that the comprehensive measures could effectively alleviate the problem of emergency overcrowding, and improve the medical environment and medical quality.

Objective:To assess the cardiac autonomic nervous function in elderly patients with frailty.Methods:Patients aged ≥ 65 years old admitted in Beijing Hospital from September 2018 to August 2019 were enrolled in this study. Clinical frailty score was used to assess the frailty. The cardiac autonomic modulation was evaluated by sinus heart rate turbulence analysis through 24 h electrocardiogram recording.Results:A total of 129 elderly patients were finally enrolled in this study with a mean age of (77.5±6.4) years, 58.1% of them were male. There were 53 patients in frail group and 76 patients in non-frail group. The age of the frailty group was significantly higher than that of the non-frailty group [(80.5±5.5) vs.(75.3±6.2)]; the prevalence of hypertension [84.9%(45/53)], heart failure [32.1%(17/53)] and peripheral vascular diseases [32.1%(17/53)] in the frailty group was significantly higher than that in the non-frailty group [65.8%(50/76), 1.3%(1/76), 17.1%(13/76); t=5.001, χ 2=5.879, 24.606, 3.921; all P<0.05]. Compared with non-frailty group, turbulence onset (TO) [-0.05(-0.92, 0.82)% vs. -0.74(-1.58, 0)%; Z=2.616, P=0.009] was significantly higher in frailty group, while turbulence slope (TS) [2.34(1.30, 5.00)ms/RR vs. 4.34(2.66, 6.39)ms/RR; Z=-3.048, P=0.002] was significantly lower. The rate of TO abnormality [49.1% (26/53) vs. 26.3%(20/76), χ 2=7.038, P=0.008] and TS abnormality [34.7%(29/53) vs. 21.0%(16/76); χ 2=15.579, P<0.001] in the frailty group was significantly higher than that in the non-frailty group. Multivariate logistic regression analysis showed that TO abnormality( OR=2.970, P=0.010, 95 %CI:1.300-6.785) and TS abnormality( OR=3.618, P=0.003, 95 %CI:1.565-8.364) were correlated with frailty. Conclusion:Cardiac autonomic nerve function may be impaired in elderly frail patients, and decreased vagal nerve tension may be presented.

Coptidis Rhizoma-Evodia Fructus is a classic herb pair in traditional Chinese medicine prescriptions, the famous prescription is called Zuojinwan, which comes from Danxi Xinfa, is composed of Coptidis Rhizoma-Evodia Fructus (6∶1). In this formula, Coptidis Rhizoma has the effect of clearing heat and drying diuresis, purging fire to remove toxin and clearing heart. Evodia Fructus has the effects of expelling cold and alleviating pain, checking upward adverse flow of Qi tostop vomiting, and assisting yang to stop diarrhea. Coptidis Rhizoma has the properties of bitter and cold, and Evodia Fructus has the properties of pungent and calidus. Pungent drugs have divergent effects, and bitter drugs have sedimentation effect, when used in combination, they can clear the liver and purge fire, calm the adverse-rising energy and stop vomiting. On the basis of Zuojinwan, Coptidis Rhizoma-Evodia Fructus medicine has derived different compatibility ratios. Different ratios are different in terms of efficacy, usage, clinical application. Although with the application of modern analytical instruments and the development of molecular pharmacology theory, the chemical constituents and Pharmacological effects of Coptidis Rhizoma and Evodia Fructus have been fully studied, as to the principle of compatibility, and the study of pharmacological effects and chemical constituents after the compatibility of the two drugs in different proportions, there is still no comprehensive system summary. This article makes a systematic and comprehensive explanation of Coptidis Rhizoma-Evodia Fructus from the aspects of famous literature, chemical composition, pharmacological effects and clinical applicationthrough querying literature and ancient books. In order to make this herb pair more standardized, and provide reference materials for further research and development for this herb pair.

To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.

Objective To evaluate the effectiveness of single nucleotide polymorphism （SNP） genoty-ping in combination with identity by state （IBS） strategy in full sibling testing. Methods Thirty-five blood samples were collected from a four-generation family. Ninety autosomal SNPs were genotyped using Precision ID Identity Panel. The distribution of IBS scores for full siblings and other relationships were calculated and compared. The relationships were determined using Fisher discriminant function and threshold method, respectively. Results Based on family members and previous research, 44, 30, 111, 71 and 1 000 pairs of full siblings （FS）, grandparent-grandchild （GG）, uncle/aunt-nephew/niece （UN）, first cousins （FC） and unrelated individuals （UI） were obtained, respectively. The average IBS scores were 148, 130, 132, 124 and 120, respectively. Except for the GG and UN pairs, the distribution differences among the other relationships had statistical significance （P<0.05）. The false rates of Fisher discriminant function to determine relationships were 1.3%, 22.3%, 17.0% and 38.7% for FS, GG, UN and FC, respectively. Based on the simulation data, the thresholds t₁=128 and t₂=141 were recommended to determine full sibling relationships （the false rate ≤0.05%）. Conclusion The 90 SNP genetic markers included in the Precision ID Identity Panel meet the testing requirements for full sibling relationships. The threshold method based on IBS has a relatively lower false rate and is more flexible.
Genotype ; Genotyping Techniques/methods* ; Humans ; Polymorphism, Single Nucleotide/genetics* ; Siblings