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The sequential occurrence of three layers of smooth muscle layers (SML) in human embryos and fetus is not known. Here, we investigated the process of gut SML development in human embryos and fetuses and compared the morphology of SML in fetuses and neonates. The H&E, Masson trichrome staining, and Immunohistochemistry were conducted on 6–12 gestation week human embryos and fetuses and on normal neonatal intestine. We showed that no lumen was seen in 6–7th gestation week embryonic gut, neither gut wall nor SML was developed in this period. In 8–9th gestation week embryonic and fetal gut, primitive inner circular SML (IC-SML) was identified in a narrow and discontinuous gut lumen with some vacuoles. In 10th gestation week fetal gut, the outer longitudinal SML (OL-SML) in gut wall was clearly identifiable, both the inner and outer SML expressed α-SMA. In 11–12th gestation week fetal gut, in addition to the IC-SML and OL-SML, the muscularis mucosae started to develop as revealed by α-SMA immune-reactivity beneath the developing mucosal epithelial layer. Comparing with the gut of fetuses of 11–12th week of gestation, the muscularis mucosae, IC-SML, and OL-SML of neonatal intestine displayed different morphology, including branching into glands of lamina propria in mucosa and increased thickness. In conclusions, in the human developing gut between week-8 to week-12 of gestation, the IC-SML develops and forms at week-8, followed by the formation of OL-SML at week-10, and the muscularis mucosae develops and forms last at week-12.
The selection of high-quality sperms is critical to intracytoplasmic sperm injection, which accounts for 70–80% of in vitro fertilization (IVF) treatments. So far, sperm screening is usually performed manually by clinicians. However, the performance of manual screening is limited in its objectivity, consistency, and efficiency. To overcome these limitations, we have developed a fast and noninvasive three-stage method to characterize morphology of freely swimming human sperms in bright-field microscopy images using deep learning models. Specifically, we use an object detection model to identify sperm heads, a classification model to select in-focus images, and a segmentation model to extract geometry of sperm heads and vacuoles. The models achieve an F1-score of 0.951 in sperm head detection, a z-position estimation error within ±1.5 μm in in-focus image selection, and a Dice score of 0.948 in sperm head segmentation, respectively. Customized lightweight architectures are used for the models to achieve real-time analysis of 200 frames per second. Comprehensive morphological parameters are calculated from sperm head geometry extracted by image segmentation. Overall, our method provides a reliable and efficient tool to assist clinicians in selecting high-quality sperms for successful IVF. It also demonstrates the effectiveness of deep learning in real-time analysis of live bright-field microscopy images.
The horse played a crucial role in China through the first millennium BC, used both for military advantage and, through incorporation into elite burials, to express social status. Details of how horses were integrated into mortuary contexts during the Qin Empire, however, are poorly understood. Here, the authors present new zooarchaeological data for 24 horses from an accessory pit in Qin Shihuang's mausoleum, indicating that the horses chosen were tall, adult males. These findings provide insights into the selection criteria for animals to be included in the emperor's tomb and invite consideration of questions concerning horse breeds, husbandry practices, and the military and symbolic importance of horses in early imperial China.
The Lancang-Mekong River Basin (LMRB) is Asia's most important transboundary river. The precipitation-dependent agriculture and the world's largest inland fishery in the basin feed more than 70 million people. Floods are the main natural disasters which pose a serious threat to the local agriculture and human life. In the future, climate change will affect the streamflow and lead to changes in flood events. Based on the GMDF and GCM data, the SPI and the VIC model were used to assess the impact of climate change on streamflow and flood events during the historical (1985–2016) and future periods (2020–2050) in the LMRB. The results show that the LMRB will become more humid in the future and annual precipitation will change from about -2 to 6 per cent under RCP4.5 and RCP8.5. In the future, this basin should experience a higher flood risk, with more flood events and a relative increase in the flood peak and frequency reaching up to +15 and +58 per cent, respectively. This study contributes to improve our understanding of the role of climate change on streamflow and flood events and provides a scientific reference for the development of local water resources management in the LMRB.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
Aims
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
Method
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
Results
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
Conclusions
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Numerous technologies have contributed to the recent development of agriculture, especially the advancement in hyperspectral remote sensing (HRS) constituted a revolution in crop monitoring. The widespread use of HRS to obtain crop parameters suggests the need for a review of research advances in this area. HRS offers new theories and methods for studying crop parameters, but much work needs to be done both experimentally and theoretically before we can truly understand the physical and chemical processes that predict these crop parameters. The study focuses on the following elements: 1) The article provides a relatively comprehensive introduction to HRS and how it can be applied to crop monitoring; 2) Current state-of-the-art techniques are summarized and analyzed to inform further advances in crop monitoring; 3) Opportunities and challenges for crop monitoring applications using HRS are discussed, and future research is summarized. Finally, through a comprehensive discussion and analysis, the article proposes new directions for using HRS to study crop characteristics, such as new data mining techniques including deep learning provide opportunities for efficient processing of large amounts of HRS data; combining the temporal and dynamic characteristics of crop parameters and vegetation growth processes will greatly improve the accuracy of crop parameter detection and monitoring; multidata fusion and multiscale data assimilation will become HRS monitoring. Multidata fusion and multiscale data assimilation will become another research hotspot for HRS monitoring of crop parameters.
Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.
Methods
In this study, unmedicated female patients with OCD (ages 8–21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.
Results
Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.
Conclusions
Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.
We aim to examine the relation of several folate forms (5-methyltetrahydrofolate (5-mTHF), unmetabolised folic acid (UMFA) and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18 757 participants from National Health and Nutrition Examination Survey 2011–2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 ml/min/1·73 m2), microalbuminuria (albumin:creatinine ratio (ACR) of 30–299 mg/g) and macroalbuminuria (ACR ≥ 300 mg/g). Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0·71; 95 % CI: 0·57, 0·87) and macroalbuminuria (OR, 0·65; 95 % CI: 0·46, 0·91) in participants in quartiles 3–4 (v. quartiles 1–2; both Pfor trend across quartiles <0·05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartiles 2–4 (v. quartile 1; OR, 2·12; 95 % CI: 1·45, 3·12; Pfor trend <0·001) and higher prevalence of macroalbuminuria in participants in quartile 4 (v. quartiles 1–3; OR, 1·46; 95 % CI: 1·06, 2·01; Pfor trend <0·001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all Pfor trend <0·01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, was associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.
Manganese (Mn) oxides have been prevalent on Earth since before the Great Oxidation Event and the Mn cycle is one of the most important biogeochemical processes on the Earth's surface. In sunlit natural environments, the photochemistry of Mn oxides has been discovered to enable solar energy harvesting and conversion in both geological and biological systems. One of the most widespread Mn oxides is birnessite, which is a semiconducting layered mineral that actively drives Mn photochemical cycling in Nature. The oxygen-evolving centre in biological photosystem II (PSII) is also a Mn-cluster of Mn4CaO5, which transforms into a birnessite-like structure during the photocatalytic oxygen evolution process. This phenomenon draws the potential parallel of Mn-functioned photoreactions between the organic and inorganic world. The Mn photoredox cycling involves both the photo-oxidation of Mn(II) and the photoreductive dissolution of Mn(IV/III) oxides. In Nature, the occurrence of Mn(IV/III) photoreduction is usually accompanied with the oxidative degradation of natural organics. For Mn(II) oxidation into Mn oxides, mechanisms of biological catalysis mediated by microorganisms (such as Pseudomonas putida and Bacillus species) and abiotic photoreactions by semiconducting minerals or reactive oxygen species have both been proposed. In particular, anaerobic Mn(II) photo-oxidation processes have been demonstrated experimentally, which shed light on Mn oxide emergence before atmospheric oxygenation on Earth. This review provides a comprehensive and up-to-date elaboration of Mn oxide photoredox cycling in Nature, and gives brand-new insight into the photochemical properties of semiconducting Mn oxides widespread on the Earth's surface.
We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59·5 (sd, 7·4) years, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4·8 × 109/l, OR 1·44; 95 % CI 1·00, 2·06), compared with those in quintiles 1–4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, the new-onset proteinuria risk was reduced from 5·2 to 2·8 % (OR 0·49; 95 % CI 0·29, 0·82) among participants with higher neutrophil counts (≥4·8 × 109/l), whereas there was no significant effect among those with neutrophil counts <4·8 × 109/l. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51 % with folic acid treatment.
The associations between sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption and the risk of metabolic syndrome (MetS) remain controversial. A quantitative assessment of dose–response associations has not been reported. This study aims to assess the associations between the risk of MetS and SSB, ASB, and total sweetened beverage (TSB, the combination of SSB and ASB) consumption by reviewing population-based epidemiological studies.
Design:
Meta-analysis.
Setting:
We searched PubMed, Embase and Web of Science databases prior to 4 November 2019, for relevant studies investigating the SSB–MetS and ASB–MetS associations. A random effects model was used to estimate pooled relative risks (RR) and 95 % CI. Dose–response association was assessed using a restricted cubic splines model.
Participants:
We identified seventeen articles (twenty-four studies, including 93 095 participants and 20 749 MetS patients).
Results:
The pooled RR for the risk of MetS were 1·51 (95 % CI 1·34, 1·69), 1·56 (1·32, 1·83) and 1·44 (1·19, 1·75) in high consumption group of TSB, SSB and ASB, respectively; and 1·20 (1·13, 1·28), 1·19 (1·11, 1·28) and 1·31 (1·05, 1·65) per 250 ml/d increase in TSB, SSB and ASB consumption, respectively. Additionally, we found evidence of non-linear, TSB–MetS and SSB–MetS dose–response associations and a linear ASB–MetS dose–response association.
Conclusions:
TSB, SSB and ASB consumption was associated with the risk of MetS. The present findings provide evidence that supports reducing intake of these beverages to lower the TSB-, SSB- and ASB-related risk of MetS.
The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak.
Methods
We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents.
Results
There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th–26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5–371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%–2.3%). The epidemic phase (27th January–15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI −40.4 to −14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February–31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility.
Conclusions
During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.
During previous pandemic outbreaks, medical staff have reported high levels of psychological distress. The aim of the current study was to report a snapshot of the psychological impact of the coronavirus disease 2019 (COVID-19) pandemic and its correlated factors on medical staff in Guangdong, China.
Methods
On the 2nd and 3rd February 2020, soon after the start of the COVID-19 pandemic, we surveyed medical staff at four hospitals in Guangdong, China, to collect demographic characteristics, Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS-14), and Insomnia Severity Index (ISI) scores.
Results
Complete responses were received from 1045 medical staff. Respondents were divided into high- and low-risk groups according to their working environment of contacting with potential or confirmed COVID-19 cases. The proportion of staff with anxiety (55.4% v. 43.0%, p < 0.001) or depression (43.6% v. 36.8%, p = 0.028) was significantly higher in the high-risk group than the low-risk group. The percentage of staff with severe anxiety was similar in the two groups. Doctors were more susceptible to moderate-to-severe depressive symptoms. The high-risk group had higher levels of clinical insomnia (13.5% v. 8.5%, p = 0.011) and were more likely to be in the upper quartile for stress symptoms (24.7% v. 19.3%, p = 0.037) than the low-risk group. Additionally, work experience negatively correlated with insomnia symptoms.
Conclusions
It is important for hospitals and authorities to protect both the physical and psychological health of medical staff during times of pandemic, even those with a low exposure risk.
The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child–Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.
We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (<818·9 μmol/l). Similar trends were found in males and females. Higher plasma Mg levels were associated with a decreased risk of new-onset hyperuricaemia in hypertensive adults.
Eating disorders have increasingly become a public health concern globally. This study aimed to reveal the burden of eating disorders at the global, regional and national levels using the Global Burden of Disease (GBD) Study 2017 data.
Methods
We extracted the age-standardised rates (ASRs) of prevalence and disability-adjusted life years (DALYs) and their 95% uncertainty intervals (UIs) of eating disorders, including anorexia nervosa and bulimia nervosa, between 1990 and 2017 from the GBD 2017 data. The estimated annual percentage changes (EAPCs) were calculated to quantify the secular trends of the burden of eating disorders.
Results
The ASRs of prevalence and the DALYs of eating disorders continuously increased worldwide from 1990 to 2017 by an average of 0.65 (95% UI: 0.59–0.71) and 0.66 (95% UI: 0.60–0.72), respectively. The burden of eating disorders was higher in females than in males, but the increment in ASRs was greater in males than in females over time. In 2017, the highest burden of eating disorders was observed in the high sociodemographic index (SDI) regions, especially Australasia (ASR of prevalence = 807.13, 95% UI: 664.20–982.30; ASR of DALYs = 170.74, 95% UI: 113.43–244.14, per 100 000 population), Western Europe and high-income North America. However, the most significant increment of the burden of eating disorders was observed in East Asia (EAPC for prevalence = 2.23, 95% UI: 2.14–2.32; EAPC for DALYs = 2.22, 95% UI: 2.13–2.31), followed by South Asia. An increasing trend in the burden of eating disorders at the national level was observed among most countries or territories. The countries with the top three highest increasing trends were Equatorial Guinea, Bosnia and Herzegovina and China. Positive associations were found between the burden estimates and the SDI levels in almost all geographic regions during the observed 28-year period. We also found that the human development indexes in 2017 were positively correlated with the EAPCs of the ASRs of prevalence (ρ = 0.222, P = 0.002) and DALYs (ρ = 0.208, P = 0.003).
Conclusion
The highest burden of eating disorders remains in the high-income western countries, but an increasing trend was observed globally and in all SDI-quintiles, especially in Asian regions that were highly populous. These results could help governments worldwide formulate suitable medical and health policies for the prevention and early intervention of eating disorders.
Take-away milk tea (TAMT) is popular among young generation, and the numbers of retails of TAMT have increased dramatically in recent years in many cities in China. Non-dairy cream is one of the major ingredients of TAMT. Concerns have been raised whether trans-fat originated from non-dairy cream may have an influence on cardio-metabolic traits. We evaluated the associations between daily intake of TAMT with plasma lipid profiles among young Chinese adults, who are the major customers of TAMT retailers.
Materials and Methods
The study population was from the phase 1 sample (104 adults) of the Carbohydrate Alternatives and Metabolic Phenotypes study. Those lacking blood samples or with a body mass index less than 18.5 kg/m2 were excluded, therefore, a total of 88 subjects with an average age of 22.8 years were included in the analysis. A food frequency questionnaire with 27 items was used to collect the dietary intake. Generalized linear regression was used to evaluate the associations between TAMT intake and cholesterol levels.
Results
The estimated mean (± SE) of TAMT intake was 14.4 ± 3.4 ml/day, with apparent differences between males (8.8 ± 2.7 ml/day) and females (17.7 ± 5.1 ml/day). The mean of total cholesterol of the participants was 4.1 ± 0.1 mmol/L. After adjusted for age, sex, education attainment, smoking status, alcohol drink habit, and physical activity level, daily TAMT intake was positively associated with total cholesterol (beta ± SE = 0.0053 ± 0.0020, P = 0.011). The association was not substantially changed with further adjustment of body fat percentage (beta ± SE = 0.0053 ± 0.0020, P = 0.010). Similar associations were observed for high/low density lipoprotein cholesterols. When analysis was performed by sex, the association was only observed among females (beta ± SE = 0.0049 ± 0.0022, P = 0.031), but not in males (beta ± SE = 0.0022 ± 0.0060, P = 0.703).
Conclusion
In young adult Chinese, we observed an association between TAMT intake with plasma cholesterol level, independent of body adiposity.
Cinnamomum chago is a woody species of the family Lauraceae endemic to Yunnan province, China, previously known from only one location, and categorized as a Plant Species with Extremely Small Population. We surveyed to determine the distribution and population size of C. chago, characterize its habitat, identify any threats, assess its conservation status, and provide guidelines for its management and conservation. During 2014–2017 we found only 64 mature C. chago, in five locations. These small, fragmented populations occur along Lancang River in Dali Prefecture at altitudes of 2,200–2,400 m. The species' extent of occurrence is c. 923 km2, with an area of occupancy of c. 60 km2. The habitat of the species has been degraded by expansion of pastoral activities and deforestation. We recommend categorization of C. chago as Endangered on the IUCN Red List, prevention of the collection of seeds and wood of the species, protection and monitoring, and ex situ propagation for future reintroductions.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.