The evolutionary history of hepaciviruses.

In the search for natural reservoirs of hepatitis C virus (HCV), a broad diversity of non-human viruses within the Hepacivirus genus has been uncovered. However, the evolutionary dynamics that shaped the diversity and timescale of hepaciviruses evolution remain elusive. To gain further insights into the origins and evolution of this genus, we screened a large dataset of wild mammal samples (n = 1,672) from Africa and Asia, and generated 34 full-length hepacivirus genomes. Phylogenetic analysis of these data together with publicly available genomes emphasizes the importance of rodents as hepacivirus hosts and we identify 13 rodent species and 3 rodent genera (in Cricetidae and Muridae families) as novel hosts of hepaciviruses. Through co-phylogenetic analyses, we demonstrate that hepacivirus diversity has been affected by cross-species transmission events against the backdrop of detectable signal of virus-host co-divergence in the deep evolutionary history. Using a Bayesian phylogenetic multidimensional scaling approach, we explore the extent to which host relatedness and geographic distances have structured present-day hepacivirus diversity. Our results provide evidence for a substantial structuring of mammalian hepacivirus diversity by host as well as geography, with a somewhat more irregular diffusion process in geographic space. Finally, using a mechanistic model that accounts for substitution saturation, we provide the first formal estimates of the timescale of hepacivirus evolution and estimate the origin of the genus to be about 22 million years ago. Our results offer a comprehensive overview of the micro- and macroevolutionary processes that have shaped hepacivirus diversity and enhance our understanding of the long-term evolution of the Hepacivirus genus.

[Secular trends of age at menarche and age at menopause in women born since 1951 from a county of Shandong Province, China].

OBJECTIVE: To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province. METHODS: Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression. RESULTS: The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66). CONCLUSION: The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.

[Association between HULC gene locus rs7763881 polymorphism and recurrence and metastasis after radical resection in hepatocellular carcinoma].

Objective: To investigate the association between the expression of long non-coding RNA genes and the HULC rs7763881 polymorphism, recurrence, and metastasis after radical resection in patients with hepatocellular carcinoma (HCC). Methods: Paraffin tissue samples were selected from 426 cases diagnosed with HCC between January 2004 to January 2012. The expression of different genotypes of HULC gene locus rs7763881 in paraffin tissues was detected by PCR, and the association between different genotype expressions and clinical case characteristics of HCC [gender, age, TNM stage, alpha-fetoprotein, tumor maximum diameter (cm), vascular invasion, tumor capsule, tumor grade] was analyzed. Cox proportional risk regression model was used to analyze the correlation between different genotypes and clinicopathological features, prognosis, and recurrence. Survival analysis between different genotypes was performed using the Kaplan-Meier method for a parallel log-rank test. Results: There were 27 (6.3%) cases in the whole group who lost to follow-up. A total of 399 (93.7%) specimens were included in the study, and 105 (26.3%), 211 (52.9%) and 83 (20.8%) were included in the rs77638881 AA, AC, and CC genotypes, respectively. Kaplan-Meier curve showed that the postoperative overall survival and recurrence-free survival rate were significantly higher in patients with the AA than AC/CC genotype (P < 0.05). Univariate analysis showed that the AC/CC genotype was closely related to tumor vascular invasion and recurrence or metastasis of HCC (P < 0.05). Cox multivariate analysis results showed that patients with the AA genotype were taken as references, and the results showed that the risk of recurrence and metastasis in patients with the CA/CC genotype increased to varying degrees, with statistical significance (P < 0.05). Conclusion: The rs7763881 polymorphic loci located on the HULC gene are closely related to HCC recurrence and metastasis after radical resection. Thus, it may be an indicator for evaluating HCC recurrence and metastasis.

Ultra-high-resolution observations of persistent null-point reconnection in the solar corona.

Magnetic reconnection is a key mechanism involved in solar eruptions and is also a prime possibility to heat the low corona to millions of degrees. Here, we present ultra-high-resolution extreme ultraviolet observations of persistent null-point reconnection in the corona at a scale of about 390 km over one hour observations of the Extreme-Ultraviolet Imager on board Solar Orbiter spacecraft. The observations show formation of a null-point configuration above a minor positive polarity embedded within a region of dominant negative polarity near a sunspot. The gentle phase of the persistent null-point reconnection is evidenced by sustained point-like high-temperature plasma (about 10 MK) near the null-point and constant outflow blobs not only along the outer spine but also along the fan surface. The blobs appear at a higher frequency than previously observed with an average velocity of about 80 km s-1 and life-times of about 40 s. The null-point reconnection also occurs explosively but only for 4 minutes, its coupling with a mini-filament eruption generates a spiral jet. These results suggest that magnetic reconnection, at previously unresolved scales, proceeds continually in a gentle and/or explosive way to persistently transfer mass and energy to the overlying corona.

[Correlation between intrahepatic triglyceride content quantified by proton magnetic resonance spectroscopy and glucose metabolism].

Objective: To investigate the correlation between intrahepatic triglyceride content (IHTC) and glucose metabolism in patients with non-alcoholic fatty liver disease (NAFLD) diagnosed by proton magnetic resonance spectroscopy (1H-MRS). Methods: A total of 239 subjects without diabetes mellitus were previously enrolled and underwent 1H-MRS scans. Anthropometric indexes including height, weight, waist and blood pressure, and laboratory findings as plasma glucose (PG), insulin (INS), C-peptide (CP), liver enzymes [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (GGT)] and lipid profiles were collected. According to IHTC levels, participants were divided into three groups: the non-NAFLD group (IHTC<5.56%), the mild NAFLD group (IHTC 5.56%-<33%), and the moderate and severe NAFLD group (IHTC ≥ 33%). The clinical characteristics of each group were analyzed, and the correlation between IHTC and glucose metabolism were assessed. Results: Compared with those in the non-NAFLD group, male proportion, waist, 120 min postprandial PG (PG120), CP, liver enzymes and total cholesterol (TC) levels were greater in the NAFLD group, whereas insulin sensitivity index-Cederholm (ISI-Cederholm) and high density lipoprotein cholesterol (HDL-C) levels were lower in the NAFLD groups. Subjects in the moderate and severe NAFLD group had higher levels of 120 min postprandial INS (INS120) and Stumvoll indexes, and lower ISI-Cederholm than those in the mild NAFLD group [80.37 (57.68, 112.70) mU/L vs.110.50(71.78, 172.80)mU/L, 1453(1178, 1798)vs.1737(1325, 2380), 358(297, 446) vs.441(318, 594), 2.27(2.01, 2.53) vs.2.06(1.81, 2.39), respectively, all P<0.05]. Correlation analyses showed that IHTC was significantly positively correlated with waist hip ratio (WHR), PG120, INS120, HOMA insulin resistance (HOMA-IR), Stumvoll 1st-insulin secretion, Stumvoll 2nd-insulin secretion, ALT, AST, GGT and TC (r=0.197, 0.274, 0.334, 0.162, 0.199, 0.211, 0.406, 0.361, 0.215, and 0.196, respectively, all P<0.05), and negatively correlated with ISI-Cederholm and HDL-C (r=-0.334, and-0.237, respectively, all P<0.05). Furthermore, a multiple linear stepwise regression analysis indicated that ISI-Cederholm (Standardized ß =-0.298, P<0.001) and Stumvoll 1st insulin secretion (Standardized ß = 0.164, P = 0.024) were independent factors of IHTC. Conclusions: Peripheral insulin resistance occurs in the early stage of NAFLD and becomes worse with the progression of the disease. IHTC was independently associated with insulin sensitivity and first-phase insulin secretion.

[Thyroid function of first-trimester twin pregnant women and its association with preterm delivery].

OBJECTIVE: To describe the thyroid function abnormality of first-trimester twin pregnant women according to different references, and to explore its association with preterm delivery. METHODS: Participants, first-trimester twin pregnant women, were recruited at Peking University Third Hospital from March 2017 to February 2020. The thyroid hormone reference for ordinary adults identified on the assay kits by Siemens incorporation, thyroid hormone reference specifically for singleton pregnancy established previously, and thyroid hormone reference specifically for twin pregnancy established previously were used in the description of hypothyroidism and hyperthyroidism for first-trimester twin pregnant women. Thyroid autoantibody reference identified on the assay kits by Siemens incorporation was used in the description of positive thyroid autoantibody. Multivariable log-binomial regression was conducted to examine the association between thyroid function and preterm delivery, in which normal pregnant women according to the three references and normal pregnant women according to twin pregnancy reference accompanied with negative thyroid autoantibody were taken as control respectively. RESULTS: A total of 570 twin pregnant women were finally included. Rates of hypothyroidism according to the three references were 1.2%, 1.6% and 3.5%, respectively. Rates of hyperthyroidism according to the three references were 32.6%, 18.1% and 1.1%, respectively. After adjustment for potential confounding factors, risk of preterm delivery significantly increased in pregnant women with hyperthyroidism according to the twin specific pregnancy reference [adjusted relative risk (ARR)=1.41, 95%CI: 1.14-1.75], while no significant increase was found in those with normal thyroid function according to the twin specific pregnancy reference but hyperthyroidism according to the singleton specific pregnancy reference (ARR=1.00, 95%CI: 0.81-1.25) and in those with hyperthyroidism purely according to the ordinary adult reference (ARR=1.06, 95%CI: 0.85-1.32), compared with those normal according to all the references. Risks of preterm delivery almost significantly or significantly increased in pregnant women with hypothyroidism according to the ordinary adult or singleton specific pregnancy reference (ARR=1.40, 95%CI: 0.88-2.22) and those with hypothyroidism according to the twin specific pregnancy reference (ARR=1.53, 95%CI: 1.03-2.28). Overall analysis of thyroid function according to the twin specific pregnancy reference and thyroid autoantibody showed that risks of preterm delivery almost significantly or significantly increased in pregnant women with simple hypothyroidism (ARR=1.46, 95%CI: 0.93-2.27), simple positive thyroid autoantibody (ARR=1.32, 95%CI: 1.15-1.52), and hypothyroidism accompanied with positive thyroid autoantibody (ARR=1.78, 95%CI: 1.30-2.44), compared with those normal according to the twin specific pregnancy reference with negative thyroid autoantibody. CONCLUSION: The ordinary adult reference and that of singleton pregnancy may lead to under-diagnosis of hypothyroidism and over-diagnosis of hyperthyroidism in first-trimester twin pregnant women. Compared with pregnant women with normal thyroid function, those missed in the diagnosis of hypothyroidism were at a higher risk of preterm delivery, while those over-diagnosed as hyperthyroidism had a similar risk of preterm delivery, indicating a need to develop and generalize twin-pregnancy-specific reference on common indicators of thyroid function. Moreover, the thyroid autoantibody should be taken into consideration in the prenatal diagnosis and treatment to twin pregnant women with hypothyroidism.

Molecular Subtyping of Mild Cognitive Impairment Based on Genetic Polymorphism and Gene Expression.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. OBJECTIVES: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression. METHODS: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients' peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm. RESULTS: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer's Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different. CONCLUSIONS: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients' peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application.

[Epidemic characteristics of hand, foot and mouth disease (HFMD) and the lag effect of average daily temperature on the epidemic of HFMD in Beijing].

Objective: To analyze the epidemic characteristics of hand, foot and mouth disease (HFMD) in Beijing and explore the short-term lag effect of daily average temperature on HFMD. Methods: The incidence data and meteorological data of HFMD were collected from Xicheng District, Chaoyang District, and Changping District of Beijing between January 2009 and December 2018. The dose-response relationship and short-term lag effect of temperature and HFMD incidence were explored by the distributed lag non-linear model (DNLM). Results: From 2009 to 2018, a total of 97 210 cases of HFMD were confirmed in Xicheng District, Chaoyang District, and Changping District of Beijing. The incidence rate of HFMD in Xicheng district was 71.83/100 000, which was the lowest in three districts. The total annual average incidence was 146.89/100 000 in the three districts. The cases were concentrated from May to July, with a small peak in October to November. The ratio of male to female was 1.49∶1, and the median age of the patients was 3.08 (1.89, 4.39) years old, which showed a decreasing trend in children under 6 years old (Z=-30.11, P<0.01). The DNLM showed that the cumulative relative risk (RR) curve had a bimodal distribution, with RR of 1.36 (95%CI: 1.05-1.76) and 1.35 (95%CI: 1.10-1.66), and the peak values appeared at 4 ℃ and 26 ℃, respectively. Conclusions: The incidence rate of HFMD in Xicheng was the lowest in three districts of Beijing. In addition, the incidence of HFMD is seasonal, and the incidence is higher in spring and summer than that in autumn and winter. Daily average temperature had a lag effect on HFMD, which was different between high temperature and low temperature.

[Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester].

OBJECTIVE: To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester. METHODS: A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 µmol/L), marginal deficiency (0.70-<1.05 µmol/L), and sufficiency (≥1.05 µmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 µmol/L), marginal deficiency (0.35-<0.70 µmol/L), and sufficiency (≥0.70 µmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio. RESULTS: The average retinol concentration of the pregnant women was (1.15±0.30) µmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) µmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (pm=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (pm= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001). CONCLUSION: There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

Safety and efficacy of propofol alone or in combination with other agents for sedation of patients undergoing colonoscopy: an updated meta-analysis.

The aim of this meta-analysis was to assess the efficacy and safety of propofol sedation for colonoscopy in comparison with traditional sedative agents. We performed a systematic search of PubMed, Embase, Scopus, Web of Science CENTRAL (Cochrane Central Register of Controlled Trials) and Google Scholar databases to identify eligible randomized controlled trials (RCTs) published before November 2019, and compared the effect of traditional sedative agents (TA) with the effect of propofol/propofol combined with TAs for routine colonoscopy. We included 22 eligible trials in our analysis, with a total of 2575 participants. We found strong associations between propofol use and short recovery (SMD MD, -1.15 [-1.55, -0.75], p<0.00001), procedure duration (SMD -0.28 [-0.55, -0.02], p<0.05), discharge times (SMD= -0.71 [-1.06, -0.36], p<0.0001), and sedation scores (SMD 1.29 [0.36, 2.22], p<0.05). Propofol in combination with traditional agents led to a significant decrease in discharge time compared with the discharge times of traditional sedatives alone (SMD=-0.69 [-1.07, -0.31], p<0.0004). The effects of propofol on cecal intubation rates, and occurrences of hypotension and apnea were similar to those of TAs. Our results suggest that propofol can be used as a safe alternative to TAs, and can significantly shorten procedure duration, recovery and discharge times, and improve sedation depth.

[Application of endoscopic tattooing with carbon nanoparticlet in the treatment for advanced colorectal cancer].

Objective: To explore the application of endoscopic tattooing with carbon nanoparticles in the treatment of advanced colorectal cancer (ACRC). Methods: A randomized controlled study was used. Inclusion criteria: (1) age more than 18 years old, and colorectal cancer was found for the first time and confirmed by colonoscopy and biopsy; (2) advanced colorectal cancer (preoperative TNM stage of T3/N1 or above, local unresectable lesion, M1 stage and simultaneously resectable metastatic lesion), and patients agreed to receive neoadjuvant therapy; (3) advanced colorectal cancer (TNM stage of T3/N1 or above) with simultaneous unresectable metastatic lesion, and patients refused operation and consented to chemoradiotherapy. Patients with previous abdominal surgery history, radiotherapy and chemotherapy history, urgent need for surgery or endoscopic stent placement and those with severe allergic constitution were excluded. Based on the above criteria, 120 patients diagnosed with ACRC in No.900 Hospital of the Joint Logistics Team from January 2016 to December 2017 were prospectively enrolled and randomly divided into tattoo group and non-tattoo group by random number table method. Tattoo group were tattooed within 1-7 days before chemoradiotherapy. The labeling location of the lesions: (1) if the colonoscopy could pass smoothly, 4 points were injected into the intestinal wall of the both opposite sides 1 cm cephalad and caudad of the tumor; (2) if the colorectal cavity was severely narrow and the colonoscopy could not pass, only 4 points were injected in 4 quadrants at 1 cm caudad of the tumor. Each injection point was injected with 0.1 ml carbon nanoparticles, and the size of the tumor was measured according to the range of carbon nanoparticles staining. The efficacy was evaluated after 8 weeks of chemoradiotherapy. Patients who were defined to be suitable for operation underwent operation 6 weeks after chemoradiotherapy. The following parameters were compared between two groups: lesion identification time, operation time, blood loss, distance from lesion to distal margin, the rate of first positive margin and the rate of anal sphincter preservation (rectal cancer). Among patients who had been evaluated as having no indication for surgery, those who were effective in chemoradiotherapy continued to receive chemotherapy in the original regimen; if the treatment failed, the chemotherapy regimen was replaced, and the efficacy was finally evaluated after six months [referring to the revised RECIST guidelines (version 1.1)]. Results: Three patients withdrew from this study, and 117 patients were enrolled in this study finally, including 59 cases in tattoo group and 58 cases in the non-tattoo group. There were no significant differences in baseline data between two groups (all P>0.05). All the patients had slight adverse reactions of radiotherapy and chemotherapy before operation, and could tolerate after symptomatic management without interruption of treatment. All the patients in the tattoo group had no discomfort such as fever, abdominal pain, abdominal distention, hematochezia, etc. and the intestinal mucosa could be seen clearly with black staining after being tattooed. A total of 77 patients were evaluated with surgical indications, including 39 cases in the tattoo group (tattoo-operable) and 38 cases in the non-tattoo group (non-tattoo-operatable). There were no significant differences in baseline data between the two groups (all P>0.05). Forty patients without operation indications continued chemoradiotherapy, including 20 cases in tattoo group (tattoo-inoperable) and 20 cases in non-tattoo group (non-tattoo-inoperable), whose differences in baseline data between the two groups were not significant as well (all P>0.05). No obvious edema, necrosis or abscess were found in the tattooed segments and the black spots could be seen quickly and clearly on the serosa of rectum in tattoo-operable patients. As compared to non-tattoo group, tattoo group had significantly shorter lesion identification time [(3.4±1.4) minutes vs. (11.8±3.4) minutes, t=-14.07,P<0.001], shorter operation time [(155.7±44.5) minutes vs. (177.2±30.2) minutes, t=-2.48,P=0.015], less blood loss [(101.3±36.7) ml vs.(120.2±38.2) ml, t=-2.22,P=0.029], shorter distance from lesion to distal margin [(3.7±1.0) cm vs. (4.6±1.7) cm, t=-2.20, P=0.034], while tattoo group had slightly higher rate of anal sphincter preservation [66.7%(16/24) vs. 45.5%(10/22), χ(2)=2.10,P=0.234] and lower rate of first positive resection margin [0 vs. 4.5%(1/22), χ(2)=0.62,P=0.480], but their differences were not significant. There were no significant differences in the degree of tumor differentiation and TNM stage between two groups. Patients without operative indication were evaluated for efficacy of chemoradiotherapy again after half a year. One case of complete response (CR), 8 of partial response (PR), 10 of stable disease (SD) and 1 of progressive disease (PD) were found and the improvement rate was 45.0% (9/20) in tattoo-inoperable patients. No case of CR, 6 of PR, 11 of SD and 3 of PD were found and the improvement rate was 30.0% (6/20) in non-tattoo-inoperable patients. There was no significant difference in the improvement rate between the two groups (P=0.514). Conclusions: Endoscopic tattooing with carbon nanoparticles injection is safe and reliable for colorectal tumor positioning. It can assist rapid detection of lesions during surgery after neoadjuvant treatment, perform accurate resection, significantly shorten the operation time and reduce surgical trauma; can assist colonoscopy accurately to measure the size of the lesions before and after chemoradiotherapy, and increase the means of assessing the efficacy to guide the follow-up treatment plan. This technique is worth clinical promotion and application.

Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway.

OBJECTIVE: Esophageal cancer (EC) ranks as the sixth leading cause of cancer-related mortality worldwide. Circular RNAs (circRNAs) are involved in the pathogenesis of different cancers. However, the regulatory mechanism of circ_0006168 in EC progression is still unclear. MATERIALS AND METHODS: The expression of circ_0006168, microRNA (miR)-384, and retinoblastoma binding protein 7 (RBBP7) in tumors and cells was measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The stability of circ_0006168 was analyzed after RNase R treatment. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate cell viability. Transwell assay was applied to determine cell migration and invasion. Glucose consumption and lactate production were detected using glucose detection and lactic acid detection kits. The interaction between miR-384 and circ_0006168 or RBBP7 was certified by Dual-Luciferase reporter system. Protein expression of pyruvate kinase (PK), RBBP7, S6 ribosomal protein kinase (S6K), phosphorylated S6K (p-S6K), S6, phosphorylated S6 (p-S6) was analyzed by Western blot. RESULTS: Circ_0006168 and RBBP7 were over-expressed while miR-384 was low-expressed in EC tumors and cells. The repression of circ_0006168 attenuated cell proliferation, migration, invasion, and glycolysis in EC. Of note, circ_0006168 functioned as a sponge while RBBP7 acted as a target of miR-384 in EC. Rescue experiment revealed that miR-384 inhibitor abrogated circ_0006168 silencing-induced repression on cell proliferation, migration, and invasion in EC. Meanwhile, upregulation of RBBP7 restored the inhibition of miR-384 on EC cell progression. Moreover, circ_0006168 was able to improve RBBP7 level by interacting with miR-384. Also, circ_0006168 could activate S6K/S6 pathway by regulating RBBP7 expression. CONCLUSIONS: Abundance of circ_0006168 contributes to cell proliferation, migration, invasion, and glycolysis in EC by competitively sponging miR-384 to facilitate RBBP7 expression, representing prospective targets for EC therapy.

Dynamic characteristics of AHLs-secreting strain Aeromonas sp. A-L2 and its bioaugmentation during quinoline biodegradation.

AIMS: In order to probe a more environmentally friendly method of pollutant treatment based on microbial bioaugmentation and quorum sensing (QS) effects. METHODS AND RESULTS: The dynamic characteristics and QS effects of the acylated homoserine lactones (AHLs)-secreting strain Aeromonas sp. A-L2 (A-L2), which was isolated from the activated sludge system, was discussed. According to the liquid chromatography-mass spectrometry results, N-butyryl-homoserine lactone (C4-HSL) and N-hexanoyl-homoserine lactone (C6-HSL) were the major AHLs secreted by strain A-L2, and the swarming of strain Ochrobactrum sp. LC-1 (LC-1) was induced by these compounds. The extracellular polymeric substance secretion of the strain LC-1 was mainly led by C6-HSL, and the biofilm formation ability was mainly influenced by C6-HSL or C4-HSL (60 µg l-1 ). The optimal AHLs secretion conditions of strain A-L2 were also studied. Drawing support from the AHLs-secreting strain A-L2 during quinoline degradation by strain LC-1, the degradation time was greatly shortened. CONCLUSIONS: Hence, AHLs-secreting strain A-L2 can be useful as an AHLs continuous supplier during bioaugmentation and pollutant biodegradation. SIGNIFICANCE AND IMPACT OF THE STUDY: The bioaugmentation process of strain A-L2 on quinoline biodegradation based on QS effects would lay a certain theoretical and practical significance for large-scale applications.

[Mobile terminal-based survey on the birth characteristics for Chinese newborns].

OBJECTIVE: To describe the birth characteristics for Chinese newborns, to assess the feasibility of collecting basic data on maternal and child health, and to conduct relevant epidemiological studies by using mobile terminals. METHODS: From June 2016 to January 2017, pregnant women who delivered in hospitals were recruited in 166 hospitals scattered across 23 provinces of China. The data on their maternal and child health including delivery mode, gestational age and birth weight, were collected by self-administered questionnaires embedded in a mobile application. The incidences or means of cesarean section, preterm birth, birth weight, length and head circumference were calculated and compared with recognized national data, including 2005 Growth Standards for Chinese Children Under 7 Years of Age, 2006 World Health Organization Child Growth Standards and 2014 Chinese Neonatal Birth Weight Standards by Gestational Age. RESULTS: A total of 9 986 women were investigated, among whom those aged ≥35 years accounted for 11.7% and those received well education (college and above) accounted for 70.2%. The rate of cesarean section, preterm delivery, low birth weight and macrosomia were 38.1%, 4.5%, 2.2%, and 7.8%, respectively. The means were (3.33±0.44) kg [male (3.36±0.44) kg, female (3.29±0.43) kg] for birth weight, (50.97±2.32) cm [male (51.04±2.32) cm, female (50.89±2.32) cm] for birth length, and (33.99±1.56) cm [male (34.01±1.57) cm, female (33.97±1.55) cm] for head circumference, respectively. As compared with the national data, the cesarean section rate and birth weights by gestational age for term-born neonates were similar to the latest national data in 2014, while the means of birth weight and length were obviously higher than those of the 2005 Growth Standards for Chinese Children Under 7 Years of Age and 2006 World Health Organization Child Growth Standards. CONCLUSION: As compared with the national data 10 years ago, the mean birth weights for male and female newborns were increased by 40 g and 80 g respectively and mean lengths by 0.6 cm and 1.3 cm, but changes for mean head circumferences were negligible, indicating that the physical health condition for Chinese newborns improved significantly over past 10 years and emerging information technology likely provided a new approach for epidemiological research.

[Institutional delivery rate in minority inhabited areas of China from 1996 to 2017].

Objective: To describe the secular trends of institutional delivery (ID) rate in minority inhabited areas of China from 1996 to 2017 according to national health policies. Methods: The number of live births and IDs for each county/district in 31 provinces of China were derived from the datasets collected by the Office for National Maternal & Child Health Statistics of China. Information on health policies and ethnical areas was derived from official governmental websites. The calendar years were divided into three periods: pre-program period (1996 to 1999), program implementation period (2000 to 2008) and post-program period (2009 to 2017). Minority autonomous regions, autonomous prefectures, and autonomous counties were defined as minority inhabited areas. The ethnic that a county was classified into was determined by a principle of close proximity to the name of the county or its next higher level administrative division. A total of 700 counties in minority inhabited areas were included in the analysis. Results: A total of 45 684 265 live births including 35 098 855 delivered in institutions were analyzed. The ID rate in minority inhabited areas was 37.5% (696 221/1 856 164) in 1996 and 99.2% (2 371 209/2 390 131) in 2017, with an annual growth rate of 4.7%. During the 22-years period, the ID rates in the eastern, central and western regions increased simultaneously, with the annual growth rates of 3.1%, 4.2% and 4.9% respectively. The difference between the eastern and western regions decreased steadily from 16% in 1996 to <1% in 2017 and the difference between the urban and rural areas decreased from 32.1% in 1996 to <1% in 2017. Besides, the ID rates in Tibetan and Yi inhabited areas with lower baseline levels increased 73 and 63 percentage points respectively. The number of counties with the ID rate of <96% were substantially reduced from 589 in 1996 to 72 in 2017; the 71 counties were all located in national deep poverty-stricken areas named Three Districts and Three States, predominantly involving Tibetan (58), Yi (6), Uygur (2) and Lisu (2) ethnics. Conclusion: During the past 22 years, the ID rate in minority inhabited areas in China has dramatically increased, achieving the goal of 2 020 ahead of schedule, but there remains a few western counties where ID rates are still<96%, indicating that minority inhabited western areas should be focused in developing national policies concerning institutional delivery.

Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc.

OBJECTIVE: Triple negative breast cancer is typically characterized by high malignancy, easy recurrence and metastasis, and poor prognosis. However, effective treatment for triple negative breast cancer has not yet been identified. Our research explores the underlying mechanisms of exosomes in transporting Let-7a and regulating c-Myc gene and their roles in the development of triple negative breast cancer, and to provide new ideas for targeted therapy of triple negative breast cancer. PATIENTS AND METHODS: Based on previous studies that focused on the roles of c-Myc and Let-7a in the development of triple negative breast cancer, triple negative breast cancer cell lines have been constructed by c-Myc knockout and overexpression of Let-7a, respectively, to evaluate the effects of c-Myc, and Let-7a, as well as exosomes transmitting Let-7a on the development of triple negative breast cancer. RESULTS: Let-7a, which is mediated by exosomes, inhibited proliferation, migration, and invasion of MDA-MB-231 cells by binding on the 3'UTR region of the c-Myc gene and silencing of the c-Myc expression. CONCLUSIONS: Our study revealed the role of c-Myc, Let-7a, and exosomes in the development of triple negative breast cancer, which lay the theoretical foundation for further usage of exosomes to construct tumor killing vectors and for exploring specific targets for triple negative breast cancer.

Association of elective cesarean delivery with metabolic measures in childhood: A prospective cohort study in China.

BACKGROUND AND AIMS: Cesarean delivery may increase the risk of childhood obesity, a precursor of metabolic syndrome (MetS). We aimed to investigate the association of elective cesarean delivery (ElCD) with MetS and its components in a Chinese birth cohort. METHODS AND RESULTS: This cohort included 1467 children (737 delivered by ElCD and 730 by spontaneous vaginal delivery [SVD]) who were followed up at the age of 4-7 years in 2013. MetS was defined as the presence of ≥3 components: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL), high fasting glucose, and hypertension. Of the 1467 children, 93 (6.3%) were categorized as having MetS: 50 (6.8%) delivered by ElCD and 43 (5.9%) by SVD. After multivariable adjustment, ElCD was not associated with MetS (adjusted odds ratio [AOR] 1.15, 95% confidence interval [CI] 0.74, 1.78) or certain components including hypertriglyceridemia, low HDL, and high fasting glucose but was associated with central obesity (AOR 1.33, 95% CI 1.02, 1.72) and hypertension (AOR 1.50, 95% CI 1.15, 1.96), as well as higher levels of total cholesterol (3.43 vs. 3.04 mmol/L; P < 0.001), low-density lipoprotein-cholesterol (1.77 vs. 1.67 mmol/L, P = 0.002), fasting glucose (5.08 vs. 5.02 mmol/L, P = 0.022), systolic (97.57 vs. 94.69 mmHg, P < 0.001)/diastolic blood pressure (63.72 vs. 62.24 mmHg, P < 0.001), and BMI (15.46 vs. 14.83 kg/m2, P < 0.001) than SVD. CONCLUSIONS: ElCD is not associated with MetS in early to middle childhood but is associated with its components including central obesity and hypertension, as well as various continuous indices.