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Object. To identify and explore the key transcription factors in hepatocellular carcinoma (HCC) progression. Methods. Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results. Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion. This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.

In the past few years, the prediction models have shown remarkable performance in most biological correlation prediction tasks. These tasks traditionally use a fixed dataset, and the model, once trained, is deployed as is. These models often encounter training issues such as sensitivity to hyperparameter tuning and "catastrophic forgetting" when adding new data. However, with the development of biomedicine and the accumulation of biological data, new predictive models are required to face the challenge of adapting to change. To this end, we propose a computational approach based on Broad learning system (BLS) to predict potential disease-associated miRNAs that retain the ability to distinguish prior training associations when new data need to be adapted. In particular, we are introducing incremental learning to the field of biological association prediction for the first time and proposed a new method for quantifying sequence similarity. In the performance evaluation, the AUC in the 5-fold cross-validation was 0.9400 +/- 0.0041. To better assess the effectiveness of MISSIM, we compared it with various classifiers and former prediction models. Its performance is superior to the previous method. Besides, the case study on identifying miRNAs associated with breast neoplasms, lung neoplasms and esophageal neoplasms show that 34, 36 and 35 out of the top 40 associations predicted by MISSIM are confirmed by recent biomedical resources. These results provide ample convincing evidence of this approach have potential value and prospect in promoting biomedical research productivity.

Supplemental Digital Content is available in the text., Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan–Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan–Meier analyses of 178 HCC samples revealed that nuclear PGAM2’s high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2’s high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.

Clinical reports of multiple primary malignant tumors (MPMTs) in the digestive system are increasing. In China, although the survival rate of patients with MPMTs is increasing, the quality of life is very low. Many patients have reached the advanced stage when the second primary tumor is found, resulting in no early intervention and treatment. This is due to the misunderstanding of MPMTs by clinicians, who treat such tumors as metastases. Therefore, before a patient has a second primary tumor, doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient.To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization.A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively. They were divided into metachronous MPMT and synchronous MPMT groups, and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted. Sex and age differences between metachronous and synchronous tumors were tested by the chi square test andAmong the 1902 patients with MPMTs confirmed by pathology, 1811 (95.2%) cases were secondary primary cancers, 89 (4.7%) cases were tertiary primary cancers, and 2 (0.1%) cases were quaternary primary cancers. Most (88.2%) of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer. The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows: Breast cancer, thyroid cancer, nonuterine cancer, lung cancer, colon cancer, kidney cancer, uterine cancer, bladder cancer, rectal cancer, and gastric cancer. The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer (11.6%), the highest incidence rate of the second primary cancer was still lung cancer (24.9%), the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer (32.7%), and the highest incidence rate of the second primary cancer was lung cancer (20.8%). Among them, breast cancer, nonuterine cancer and uterine cancer were female-specific malignant tumor types, and thyroid cancer also accounted for 79.6% of female patients. The top five metachronous cancer combinations, independent of female-specific malignant tumor types and thyroid cancer, were colon cancer and lung cancer (26 cases), kidney cancer and lung cancer (25 cases), rectal cancer and lung cancer (20 cases), gastric cancer and lung cancer (17 cases), and bladder cancer and lung cancer (17 cases). The most common synchronous cancer combination was colon cancer and rectal cancer (15 cases).Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

In this work, 26 methylated acylphloroglucinol meroterpenoids with diverse skeletons, including 18 new ones (bellumones A-R, 1-18), were identified from the flowers of Hypericum bellum. Their structures including absolute configurations were elucidated by detailed spectroscopic data, calculated electronic circular dichroism (ECD), and X-ray diffraction (XRD). Through methylation at C-5, prenylation with different chain lengths of the acylphloroglucinol-derived core, along with different types of secondary cyclization, type A bicyclic polyprenylated acylphloroglucinols (BPAPs) (1-5 and 19-24) and dearomatized isoprenylated acylphloroglucinols (DIAPs) (6-18 and 25-26) were obtained. The significant results of anti-inflammatory, antioxidant, and anti-nonalcoholic steatohepatitis (anti-NASH) activities suggest its usefulness in daily health care.

Three unprecedented benzoyl-migrated polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforones A–C (1–3), were isolated from Hypericum forrestii, together with a new benzoyl-substituted analogue (4) of hyperforin. Compounds 1–3 are the first examples of naturally occurring benzoyl-PPAPs with a unique C-1 H-substituted bicyclo[5.3.1]hendecane scaffold. Their structures and absolute configurations were established by HRESIMS, NMR spectroscopy data, electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and gauge-independent atomic orbital (GIAO) NMR calculations with DP4+ analyses. A plausible biosynthetic formation of the benzoyl-migrated C-1 H-substituted bicyclo[5.3.1]hendecane skeleton in 1–3via a sterically favored hemiketalization/Retro-Claisen cascade was proposed. Bzhyperforin (4) showed significant cytotoxicity against MDA-MB-231 cells with an IC50 value of 6.88 ± 1.37 μM.

As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions.Como consecuencia del rápido aumento del número de pacientes que se han recuperado de la COVID-19 en todo el mundo, es necesario cambiar el enfoque de la detección rápida del patógeno, el tratamiento y la prevención para promover una mejor recuperación. A pesar de la escasez de nuestros conocimientos, estudios recientes han desvelado una plétora de consecuencias pulmonares y sistémicas que requieren atención médica. Estas consecuencias se mantienen al final del seguimiento, que oscila entre 1 mes y 1 año. Aquí se hace una revisión de las consecuencias de la COVID-19 en términos de síntomas residuales y manifestaciones radiológicas y funcionales y se identifican los posibles factores de riesgo que contribuyen a una recuperación demorada. También se resumen los beneficios de las intervenciones clínicas (en particular el programa de rehabilitación pulmonar) y se abordan varias preocupaciones no resueltas y direcciones clave de investigación futura.

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a newly discovered mitochondrial-derived peptide with the main functions of promoting glucose metabolism and reducing adipose tissue. MOTS-c was found to be a substance that can mimic the motor effect and improve the motor ability. It is sex-related and the circulating MOTS-c level is decreased in obese males. Obesity can cause male reproductive dysfunction, while exercise can improve obesity-induced reduction of male reproductive function. This article discusses the effect of exercise intervention on the mitochondrial-derived peptide MOTS-c in the germ cells of obese men.

Objectives: Procalcitonin (PCT) has long been proved as an early diagnostic signal for postoperative outcomes. The purpose of this study is to explore the value of serum procalcitonin levels in predicting post-hepatectomy liver failure (PHLF), and further to declarethe relationship between postoperative PCT and short-term prognosis in patients after hepatectomy.Methods: Clinical data of patients with hepatocellular carcinoma (HCC) who underwent hepatectomy from June 1st, 2019 to September 31st, 2020 at Shanghai Eastern Hepatobiliary Surgery Hospital had been retrospectively analyzed. Logistic regression analysis was used to evaluate the risk factors related to PHLF. The Kaplan-Meier method was used to calculate the PHLF rate and 30-day survival after surgery.Results: A total of 885 patients with complete data were finally included in analysis, 311 of them with elevated serum PCT (≥1 ng/ml). Results of the logistic regression analysis suggested a significant association between PCT and PHLF [HR, 95%CI; 3.801 (1.825, 7.917), p < 0.001]. Other significant risk factors for PHLF included portal hypertension, portal blocking time (>30 min) and blood transfusion (>200 ml). Kaplan-Meier analysis also suggested a higher PHLF rate in elevated PCT patients [9.0% (95% CI, 7.3 to 12.8 VS. 1.9% (95% CI, 1.1–4.3)); p < 0.001]. For secondary outcomes, elevated PCT was also highly associated with postoperative sepsis, ICU admission, 30-day mortality and 3-month mortality.Conclusion: Elevated procalcitonin level in patients after hepatectomy is related to higher PHLF rate, with lower 30-day survival and poor short-term postoperative outcomes.

Sarcandra glabra (Thunb.) Nakai (Chloranthaceae), grown and cultivated evergreen shrub in south of China, has been used in traditional Chinese medicines (TCMs) to treat bruises, bone fractures and arthritis which were partly due to inflammation. Previous phytochemical and pharmacological researches indicated that flavonoids, coumarins, phenolic acids as its main anti-inflammatory ingredients related to its traditional efficacy. Our present research aimed to elucidate whether the fascinating and abundant lindenane-type sesquiterpeniods are also its anti-inflammatory components and uncover its anti-inflammatory mechanism. On the guidance of results of phytochemical fraction and anti-inflammatory activity evaluation, ten anti-inflammatory lindenane sesquiterpenes with half maximal inhibitory concentration (IC50) values from 8.13 ± 0.37 to 24.06 ± 0.60 μM, including seven dimmers (1-7) and three monomers (8-10) were discovered and characterized from the anti-inflammatory fraction of roots of title plant. Considering the activity and quantity, shizukaol D was selected as the target for further mechanism study. Firstly, shizukaol D could downregulate the expression of inducible nitric oxide synthase (iNOS) and suppress the protein level of nuclear factor kappa B (NF-κB) p65 as well as the nuclear translocation of NF-κB p65. Meanwhile, shizukaol D also decreased the level of reactive oxygen species (ROS) and enhanced the activities of phase II defense enzymes superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) by elevating the expression of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) via promoting nuclear factor E2-related factor 2 (Nrf2) activation as well as its nuclear translocation, and regulating the pathway of phosphoinositide 3-kinases (PI3K)/ protein kinase B (AKT) rather than mitogen-activated protein kinase (MAPK) to the activation of Nrf2/HO-1 signaling. Taken together, our research provided the phytochemical and pharmacological evidences for that the major sesquiterpenoid dimers can be defined as the anti-inflammatory ingredients of S.glabra and this kind of sesquiterpenoids, such as shizukaol D, can be as an attractive therapeutic candidate for inflammatory diseases.

Background The Woman’s Condom, a newly designed condom for women, has obtained market approval in China, but it remains relatively unfamiliar to the migrant population. The aim of this study is to evaluate the short-term acceptability of the Woman’s Condom and influencing factors among internal migrants. Methods A longitudinal study was conducted among 1800 migrants in Beijing, Chongqing, and Shanghai in China between August 2013 and August 2014.Three-level model was implemented with the Statistical Analysis System software (v.9.4 SAS Institute) to analyze within-individual changes, between-individuals effects, and between-group effects. Results Three-level model analysis revealed statistically higher short-term acceptability of the Woman’s Condom among subjects who lived in Shanghai (β = 6.50, t = 2.76, p β = 3.05, t = 2.76, p β = − 1.69, t = − 7.55, p β = − 2.30, t = − 1.94, p = 0.05) were negatively related, while occupations of education, health, and civil staff (β = 1.50, t = 2.92, p β = 1.09, t = 5.54, p Conclusions The findings indicate that the Woman’s Condom enjoyed relatively high short-term acceptability among migrants in China. In order to popularize the Women’s Condoms in migrants, more publicity, consultation and training in open and prosperous areas should be strengthened.

Objective: This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China. Methods: Between August 2013 and August 2015, a total of 8,669 internal migrants from four major cities in China (Beijing, Shanghai, Chengdu, and Chongqing) voluntarily participated in our study. They were interviewed, and the data on their demographic information, occupation, and sexual activities were collected. The Chi-square test and multiple logistic regressions were conducted to identify significant associations. A stepwise method was adopted for the selection of variables. Results: There were 3,597 (41.49%) males and 5,072 (58.51%) females in total. A higher percentage of males reported that they felt sexual repression compared to females (14.43% vs. 9.21%). After adjusting for other covariates, the consequence was showed that male migrants working for more than 5 days were more likely to report sexual repression (odds ratio [OR] = 1.40, P < 0.05). Living in a collective dormitory with others was also a risk factor for male migrants. The longer males spent with their partners, the less sexual repression occurred (OR= 0.94, P < 0.05). Similarly, agricultural household registration status and working for more than 5 days increased the risk for sexual repression among female migrants (OR= 1.41 and OR = 1.46, respectively, P < 0.05). Frequent and constructive communication also protected females against sexual repression (P < 0.05). Well-educated females experienced relatively less sexual repression when compared to their counterparts with less education (P < 0.05). Conclusions: Sexual repression was significantly associated with a few demographic, occupational, and sexual risk factors. Meaningful differences have been identified between male and female migrants. More effective intervention programs such as safeguard measures and welfare policies should be designed and implemented for a majority of female migrants and for those with agricultural household registration status.

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (

Tibetan red deer (Cervus wallichii) is an endemic species to China, which was once considered extinct in the wild. As there are several other wild ungulates and domestic animals with similar feeding habits within its habitat range, it's thus essential to study interspecific competition and co-existence between Tibetan red deer and other cohabiting ungulates in the highly unique environment of Qinghai-Tibet Plateau. Using microscopic analysis on fresh fecal samples collected in Sangri Tibetan Red Deer Nature Reserve from August to September in 2013 and 2014, the trophic niche width and overlap index were calculated on the basis of diet composition of C. wallichii, Cervus albirostris, Procapra picticaudata, Bos mutus and Capra hircas in green grass period. We analyzed and compared the overlap and differentiation of feeding habits between Tibetan red deer and other wild ungulates and domestic animals. The results showed that C. wallichii fed on similar edible plants with other species, but differed in proportion of different dietary components, with the main edible plants of C. wallichii being mostly the secondary edible plants to other species. Leontopodium pusillum was the common main edible plant for C. wallichii (percentage in animal recipes was 11.2%) and B. mutus (10.2%), Salix xizangensis was the common main edible plant of C. wallichii (9.6%) and C. albirostris (11.4%). At plant family level, Leguminosae was the common main edible plant family for C. wallichii (21.4%) and P. picticaudata (42.5%). Cyperaceae was the common main edible plant family for C. albirostris (49.2%), B. mutus (33.4%) and C. hircas (50.3%). Compositae was main edible plant family for C. wallichii (29.6%), as well as the secondary edible plant family for C. albirostris (7.6%), P. picticaudata (11.6%), B. mutus (17.3%) and C. hircas (14.1%). As the secondary edible plant family for C. wallichii (7.1%), Gramineae took up a lower proportion than that of the other ungulates (C. albirostris (13.6%), P. picticaudata (12.3%), B. mutus (11.5%) and C. hircas (16.0%)). Food overlap indices between C. wallichii and the other ungulates were all higher than 0.5, and the highest with B. mutus (0.65). The food diversity index (1.32), evenness index (0.37) and niche width index (15.79) of C. wallichii were all at high values. Compared with the results from 2007 to 2008, dietary composition of Tibetan red deer changed greatly as the proportion of Leguminosae increased while that of Cyperaceae decreased, resulting in improvement of food quality. In addition, there was greater competition of food resources between C. wallichii and domestic animals, which would further affect the distribution range and living space of C. wallichii.西藏马鹿为我国特有种,曾一度被认定为野外灭绝。在其生境中有多种食性相近的野生有蹄类及家畜同域分布,探究青藏高原特殊环境下西藏马鹿与这些有蹄类的食物资源种间竞争与共存关系十分必要。2013年和2014年8—9月,采用粪便显微分析法确定了桑日县西藏马鹿自然保护区西藏马鹿、白唇鹿、藏原羚、牦牛、山羊草青期食物组成,并比较分析了西藏马鹿与同域野生有蹄类、家畜之间的食物重叠和分化状况。结果表明: 西藏马鹿与其他有蹄类具有相似的可食植物种类组成,但所占食谱比例不同。西藏马鹿主要可食植物多为其他有蹄类次要可食植物,其中弱小火绒草为西藏马鹿(在动物食谱中的百分比为11.2%)与牦牛(10.2%)共同的主要食物,西藏柳为西藏马鹿(9.6%)和白唇鹿(11.4%)共同的主要食物。从科级水平来看,豆科植物为西藏马鹿(21.4%)与藏原羚(42.5%)的共同主要可食植物,莎草科植物为白唇鹿(49.2%)、牦牛(33.4%)、山羊(50.3%)的共同主要可食植物。菊科植物作为西藏马鹿(29.6%)的主要可食植物,也是白唇鹿(7.6%)、藏原羚(11.6%)、牦牛(17.3%)和山羊(14.1%)的次要可食植物。禾本科植物作为西藏马鹿(7.1%)次要可食植物,较其他4种有蹄类(白唇鹿13.6%、藏原羚12.3%、牦牛11.5%、山羊16.0%)所占比例低。西藏马鹿与其他有蹄类食物重叠度均高于0.5,与牦牛的重叠度最高(0.65)。西藏马鹿食物多样性指数(1.32)、均匀度指数(0.37)和生态位宽度指数(15.79)均较高。与2007—2008年相比,西藏马鹿食物组成变化较大,豆科植物比例增大,莎草科植物比例降低,食物质量总体有所提高。西藏马鹿与家畜之间存在较高的食物资源竞争,这将进一步影响西藏马鹿的分布范围和生存空间。.

Objective To discover critical genes contributing to the stemness and maintenance of spermatogonial stem cells (SSCs) and provide new insights into the function of the leucine-rich repeat (LRR) family member Lrrc34 (leucine-rich repeat-containing 34) in SSCs from mice. Methods Bioinformatic methods, including differentially expressed gene (DEG), gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were used to uncover latent pluripotency-related genes. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels, respectively. RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs. Results Eight DEGs between ID4-EGFP

Background: Domestic migrant populations are highly mobilized at a sexually active age, and often fail to meet their needs for contraception. Moreover, they assume sexual and reproductive health (SRH) risks and utilize fewer family planning services. Method: A quasi-experimental trial (community intervention) was adopted. Two-stage stratified cluster sampling was applied to recruit participants in Beijing and Chongqing. A comprehensive SRH/family planning intervention was implemented from August 4 2014 to August 3 2015. Propensity score matching (PSM) and multivariate probit models were adopted. Results: In total, 2100 and 2024 eligible participants were involved, and 815 and 629 pairs were matched by PSM in Beijing and Chongqing, respectively. The knowledge and attitudes of the participants regarding SRH and contraception were significantly improved through the comprehensive intervention. Reversible contraceptive methods were the most prevalent, couples largely decided to utilize condoms and family planning services. Conclusions: The comprehensive intervention had positive effects on knowledge, attitudes, and practices (KAP) for SRH/family planning among the domestic migrant population. The results acquired can be extrapolated to some extent, and the pattern of this intervention is well geared toward other similar settings in China.