Diversifying crop rotation increases food production, reduces net greenhouse gas emissions and improves soil health.

Global food production faces challenges in balancing the need for increased yields with environmental sustainability. This study presents a six-year field experiment in the North China Plain, demonstrating the benefits of diversifying traditional cereal monoculture (wheat-maize) with cash crops (sweet potato) and legumes (peanut and soybean). The diversified rotations increase equivalent yield by up to 38%, reduce N2O emissions by 39%, and improve the system's greenhouse gas balance by 88%. Furthermore, including legumes in crop rotations stimulates soil microbial activities, increases soil organic carbon stocks by 8%, and enhances soil health (indexed with the selected soil physiochemical and biological properties) by 45%. The large-scale adoption of diversified cropping systems in the North China Plain could increase cereal production by 32% when wheat-maize follows alternative crops in rotation and farmer income by 20% while benefiting the environment. This study provides an example of sustainable food production practices, emphasizing the significance of crop diversification for long-term agricultural resilience and soil health.

Genome-Resolved Metagenomics and Denitrifying Strain Isolation Reveal New Insights into Microbial Denitrification in the Deep Vadose Zone.

The heavy use of nitrogen fertilizer in intensive agricultural areas often leads to nitrate accumulation in subsurface soil and nitrate contamination in groundwater, which poses a serious risk to public health. Denitrifying microorganisms in the subsoil convert nitrate to gaseous forms of nitrogen, thereby mitigating the leaching of nitrate into groundwater. Here, we investigated denitrifying microorganisms in the deep vadose zone of a typical intensive agricultural area in China through microcosm enrichment, genome-resolved metagenomic analysis, and denitrifying bacteria isolation. A total of 1000 metagenome-assembled genomes (MAGs) were reconstructed, resulting in 98 high-quality, dereplicated MAGs that contained denitrification genes. Among them, 32 MAGs could not be taxonomically classified at the genus or species level, indicating that a broader spectrum of taxonomic groups is involved in subsoil denitrification than previously recognized. A denitrifier isolate library was constructed by using a strategy combining high-throughput and conventional cultivation techniques. Assessment of the denitrification characteristics of both the MAGs and isolates demonstrated the dominance of truncated denitrification. Functional screening revealed the highest denitrification activity in two complete denitrifiers belonging to the genus Pseudomonas. These findings greatly expand the current knowledge of the composition and function of denitrifying microorganisms in subsoils. The constructed isolate library provided the first pool of subsoil-denitrifying microorganisms that could facilitate the development of microbe-based technologies for nitrate attenuation in groundwater.

Diversity and spatiotemporal dynamics of fish communities in the Chongqing section of the upper Yangtze River based on eDNA metabarcoding.

Fish diversity plays a critical role in maintaining the balance of water ecosystems, especially in the Chongqing section of the National Nature Reserve for Rare and Endemic Fishes in the upper Yangtze River, which serves as an important habitat for rare and endemic fish, as well as an important channel for the replenishment of fishery resources in the Three Gorges Reservoir. Under a 10-year ban on fishing in the Yangtze River basin, we investigate fish diversity and seasonal variation in the Reserve by using environmental DNA (eDNA) metabarcoding. We found fishes belonging to 85 genera, 24 families, and 8 orders in the Reserve. A comparison of eDNA metabarcoding results with the diversity of a recent fish catch revealed that eDNA metabarcoding not only enables rapid and efficient fish monitoring but also has a high sensitivity. Furthermore, the study demonstrates that eDNA metabarcoding can be used as a tool for monitoring seasonal variations of fish composition in freshwater ecosystems. The alpha and beta diversity analysis both showed compositional differences in the fish community in accordance with seasonal variations. In addition, changes in eDNA relative sequence abundance and the detection of fish species at different sampling sites may reflect shifts in habitat use and distribution. Thus, we provide detailed seasonal data on fish diversity in the Chongqing section of the Reserve. This will contribute to conservation and to the understanding of fish diversity and community dynamics in the Chongqing section of the Reserve.

Effects of climate change on wind erosion in the three provinces of Northeast China.

The three provinces of Northeast China are crucial to national commodity grain production. Soils in those areas have begun to severely degrade after long-term high-intensity use, with wind erosion as one of the main reasons. Based on meteorological and soil data from 1981 to 2019, we evaluated the spatial-temporal characteristics of wind erosion on bare land in the three provinces of Northeast China by using the revised wind erosion equation (RWEQ), and analyzed the contributions of meteorological factors to wind erosion on bare land. The results showed that, the meteorological factors of wind erosion were overall high in southwestern part and low in northeastern part of the region. In general, wind erosion in the region was substantial, especially in Liaoning. During the 39 years, wind erosion significantly increased throughout the whole year and during the growing season, at a rate of 129 and 105 t·km-2 per decade, respectively. The obvious increase in wind erosion was observed in the northwest Liaoning, Liaohe Plain, and Changbai Mountain area. Wind speed and air temperature were the main factors affecting wind erosion during the year and non-growing season, which contributed less during the growing season when precipitation contributed the most. We concluded that climate change has aggravated soil wind erosion in the three provinces of Northeast China.

[Spatial Variation Characteristics, Influencing Factors, and Sources of Hydrogeochemical of Surface Water and Groundwater in Mountainous Area of Hutuo River].

Surface runoff has dropped sharply in the mountainous area of the Hutuo River, posing a huge challenge to the sustainable use of groundwater in the North China Plain (NCP). The Taihang Mountain area is the main recharge source area of groundwater in the NCP. An in-depth study of spatial variation characteristics, influencing factors, and sources of hydrogeochemical characteristics of surface water and groundwater in the mountainous area of the Hutuo River can facilitate a comprehensive understanding of regional water resource status and sustainable utilization of water resources. Based on isotopic, hydrogeochemical, and mathematical statistics methods, this study analyzed spatial variation of hydrochemical characteristics in surface water and groundwater and its sources and main controlling factors. The results showed that the river water, well water, and spring water were all recharged by atmospheric precipitation in the mountainous areas of the Hutuo River. Under the combined influence of natural factors and human factors, the hydrogeochemical characteristics of river, well, and spring water showed large spatial differences. On the whole, the hydrochemical types of mainstreams were relatively concentrated. In the upper and lower mining reach areas, the mainstream water chemical type was dominated by Ca·Mg-SO4·HCO3, whereas that in the natural vegetation area (middle reach:between Qingshui River and Longhua River) was dominated by Ca·Mg-HCO3·SO4. In the upper stream, the main hydrochemical type of the Yukou River and Ehe River tributaries was Ca·Mg-SO4·HCO3, which was consistent with that of the main stream. The main hydrochemical types of the Muma River and Qingshui River tributaries were Ca-HCO3, Ca·Mg-HCO3, and Ca·Mg-HCO3·SO4 in the midstream. The main hydrochemical types of the Mianhe River and Yehe River tributaries were Ca-SO4, Ca·Mg-SO4, and Ca·Mg-SO4·HCO3. Mineral dissolution was still the main controlling factor for the hydrochemical characteristics of surface water and groundwater in the mountainous area of the Hutuo River. The contribution rates were 69.86% and 18.84% for mineral dissolution and human activities, respectively. Therefore, in the future, water resource utilization in the upper reaches of the Hutuo River should not only consider the issue of water quantity but also a series of water environment problems such as nitrate pollution and mining pollution caused by human activities.

Identifying hotspots of water table depth change by coupling trend with time stability analysis in the North China Plain.

Many groundwater construction projects such as South-to-North Water Diversion Project (SNWDP) were conducted for controlling groundwater overexploitation in the North China Plain (NCP). However, more insight is required into the magnitude and distribution of water table depth (WTD) in time and space over the NCP. This study evaluated the variability and the hotspots of WTD based on 83 unconfined monitoring wells and took trend, breakpoint, and time stability into consideration. We found the average WTD of unconfined aquifer for the Southern Hebei Plain generally increased continuously from 1998 to 2020 in spite of the operation of the SNWDP since 2014. However, the rise rate of WTD slows down in recent years and the WTD has decreased in certain subregions. We further divided these groundwater wells into five groups: climb accelerating (Group 1), increase decelerating (Group 2), first rise then descend (Group 3), first descend then rise (Group 4), decrease decelerating (Group 5), and reduce accelerating (Group 6). Moreover, we found that the number of wells that divided into Group1 to Group 5 account for 15 %, 41 %, 25 %, 18 %, and 1 % of the total number of observation wells. The breakpoints of all the wells are from 2001 to 2017 and most of the breakpoints were found before 2014, which demonstrates that other groundwater management strategies implemented in the Southern Hebei Plain prior to the operation of the SNWDP plays a crucial part. The hotspots area for group 1 is mainly distributed in the north region of Shijiazhuang City, group 2 is in southern region of piedmont plain, group 3 is in northern region of Baoding and south-west region of Xingtai City, and group 4 is in Cangzhou City and eastern region of Xingtai City. The method and framework of this study can be applied in other regions suffering from groundwater depletion.

eDNA metabarcoding reveals differences in fish diversity and community structure in heterogeneous habitat areas shaped by cascade hydropower.

Freshwater ecosystems are under great threat from humans, among which habitat heterogeneity is the most obvious, being one of the important reasons for the decline of fish diversity. This phenomenon is particularly prominent in the Wujiang River, where the continuous rapids of the mainstream have been divided into 12 mutually isolated sections by 11 cascade hydropower reservoirs. Based on the fact that conventional survey methods are more harmful to the ecological environment, the efficient and noninvasive environmental DNA metabarcoding (eDNA) approach was used in this study to conduct an aquatic ecological survey of the 12 river sections of the mainstream of the Wujiang River. A total of 2299 operational taxonomic units (OTUs) were obtained, corresponding to 97 species, including four nationally protected fish species and 12 alien species. The results indicate that the fish community structure of the Wujiang River mainstream, which was originally dominated by rheophilic fish species, has been changed. And there are differences in fish species diversity and species composition among the reservoir areas of the mainstream of the Wujiang River. The fish species in the area have gradually declined under the influence of anthropogenic factors such as terraced hydropower and overfishing. The fish populations consequently have demonstrated a tendency to be species miniaturized, and the indigenous fish are severely threatened. In addition, the fish composition monitored by the eDNA approach was found to be close to the fish composition of historical information on the Wujiang River, indicating that eDNA approach may be used as a complementary tool to conventional methods in this basin.

Spatial and temporal variations of extreme climate index in the Songhua River Basin during 1961-2020.

Understanding climate change and extreme climate is of great significance for ensuring food security and socio-economic development of the Songhua River Basin. Based on the daily precipitation, maximum temperature and minimum temperature data during 1961-2020 from 69 meteorological stations in and around the Songhua River Basin, we analyzed the temporal and spatial variations of extreme temperature and precipitation in the Songhua River Basin using 27 extreme climate indices recommended by the World Meteorological Organization, and linear trend method, Mann-Kendall trend test and ordinary Kriging interpolation methodology. The results showed that, from 1961 to 2020, except for cold speel duration, the extreme cold index in the study area showed a downward trend, while the extreme warm index, extreme value index and other temperature indices showed an upward trend. The increasing trend of the minimum temperature was greater than that of the maximum temperature. Icing days, cold speel duration and warm speel duration showed an increasing trend from south to north, while the minimum value of maximum temperature and that of minimum temperature showed opposite spatial characteristics. The high value areas of summer days and tropical nights were mainly distributed in the southwestern region, while there was no obvious spatial variations of cool days, warm nights, and warm days. Overall, except for cold speel duration, other extreme cold indices had a rapid decreasing trend in the north and west of the Songhua River Basin. In the warm index, summer days, warm nights, warm days, and warm speel duration had a rapid upward trend in the north and west, and tropical nights had the fastest rise in the southwest. In the extreme value index, the maximum of temperature rose fastest in the northwest, while the minimum rose fastest in the northeast. Except for consecutive dry days, the rest of precipitation indices showed an increasing trend, and the fastest rising areas were mainly in the north-central part of the Nenjiang River Basin, while some areas in the south of the Nenjiang River Basin became dry. Heavy precipitation days, very heavy precipitation days, heaviest precipitation days, consecutive wet days, very wet day precipitation, extremely wet day precipitation, and annual precipitation showed a gradual decreasing pattern from southeast to northwest. Overall, the Songhua River Basin was warming and wetting, but there were some differences among different regions, especially the northern and southern parts of the Nenjiang River Basin.

Mitochondrial genomic characterization of two endemic Chinese freshwater crabs of the genus Sinopotamon (Brachyura: Potamidae) and implications for biogeography analysis of Potamidae.

As an endemic freshwater crab group in China, the phylogenetic relationships within Sinopotamon are still controversial because of the limited taxon samples. In this study, the complete mitogenomes of Sinopotamon chishuiense with 17,311 bp and the nearly complete mitogenomes of S. wushanense with 16,785 bp were firstly sequenced and analyzed. Compared with other reported mitogenomes of Potamidae, some novel patterns of gene rearrangement were detected in these two Sinopotamon mitogenomes, which could be illuminated by the mechanisms of tandem duplication-random loss, recombination, and translocation. Phylogenetic analyses showed the nonmonophyly of the Sinopotamon and a sister group relationship with Tenuilapotamon. These crabs from the eastern and southern of the Yangtze River basin were more closely related while other crabs form the plateau areas formed a separate clade. Divergence time indicated that the Sinopotamon and its sister group Tenuilapotamon diverged from other potamiscine freshwater crabs approximately 42.65 Mya, which belongs to the recent main uplifts period of the Tibetan Plateau in the Late Miocene. Combined with the similar evolutionary rates and relatively stable habitat altitude of these Sinopotamon species, these results implied that the ecological environment may be relatively stable during the speciation. Overall, our study yielded worthy perceptions for the evolutionary and taxonomic relationship of Sinopotamon and will help to better clarify the gene rearrangement events of the invertebrate mitogenome and lay the foundation for further phylogenetic study of Sinopotamon. Overall, our study yielded valuable insights into the evolutionary history and taxonomic relationship of Sinopotamon and these results will help to better explain the gene rearrangement events of the invertebrate mitogenome and lay the foundation for further phylogenetic study of Sinopotamon.

Short daylight photoperiod alleviated alarm substance-stimulated fear response of zebrafish.

Photoperiod has been well-documented to be involved in regulating many activities of animals. However, whether photoperiod takes part in mood control, such as fear response in fish and the underlying mode(s) of action remain unclear. In this study, adult zebrafish males and females (Danio rerio) were exposed to different photoperiods, Blank (12 h light: 12 h dark), Control (12 h light: 12 h dark), Short daylight (SD, 6 h light: 18 h dark) and Long daylight (LD, 18 h light: 6 h dark) for 28 days. After exposure, fear response of the fish was investigated using a novel tank diving test. After alarm substance administration, the onset to higher half, total duration in lower half and duration of freezing in SD-fish were significantly decreased, suggesting that short daylight photoperiod is capable of alleviating fear response in zebrafish. In contrast, comparing with the Control, LD didn't show significant effect on fear response of the fish. Further investigation revealed that SD increased the levels of melatonin (MT), serotonin (5-HT) and dopamine (DA) in the brain while decreased the plasma level of cortisol comparing to the Control. Moreover, the expressions of genes in MT, 5-HT and DA pathways and HPI axis were also altered consistently. Our data indicated that short daylight photoperiod might alleviate fear response of zebrafish probably through interfering with MT/5-HT/DA pathways and HPI axis.

Enlarged fins of Tibetan catfish provide new evidence of adaptation to high plateau.

The uplift of the Tibetan Plateau significantly altered the geomorphology and climate of the Euroasia by creating large mountains and rivers. Fishes are more likely to be affected relative to other organisms, as they are largely restricted to river systems. Faced with the rapidly flowing water in the Tibetan Plateau, a group of catfish has evolved greatly enlarged pectoral fins with more numbers of fin-rays to form an adhesive apparatus. However, the genetic basis of these adaptations in Tibetan catfishes remains elusive. In this study, we performed comparative genomic analyses based on the chromosome-level genome of Glyptosternum maculatum in family Sisoridae and detected some proteins with conspicuously high evolutionary rates in particular in genes involved in skeleton development, energy metabolism, and hypoxia response. We found that the hoxd12a gene evolved faster and a loss-of-function assay of hoxd12a supports a potential role for this gene in shaping the enlarged fins of these Tibetan catfishes. Other genes with amino acid replacements and signatures of positive selection included proteins involved in low temperature (TRMU) and hypoxia (VHL) responses. Functional assays reveal that the G. maculatumTRMU allele generates more mitochondrial ATP than the ancestral allele found in low-altitude fishes. Functional assays of VHL alleles suggest that the G. maculatum allele has lower transactivation activity than the low-altitude forms. These findings provide a window into the genomic underpinnings of physiological adaptations that permit G. maculatum to survive in the harsh environment of the Tibetan Himalayas that mirror those that are convergently found in other vertebrates such as humans.

Chronic exposure to environmentally relevant concentrations of carbamazepine interferes with anxiety response of adult female zebrafish through GABA /5-HT pathway and HPI axis.

Carbamazepine (CBZ) is one of the widely distributed pharmaceutical residues in aquatic environments, yet few researches have addressed its chronic effect on the anxiety of fish, and the mechanisms possibly involved remained elusive. In this study, adult female zebrafish (Danio rerio) were exposed to environmental relevant concentrations of CBZ (CBZ-low, 10 µg/L; CBZ-high, 100 µg/L) for 28 days. After exposure, CBZ-high didn't affect the anxiety of fish. However, the onset time to the higher half of the tank was delayed and the total duration in the lower half of the tank was increased in CBZ-low fish, suggesting an increased anxiety. Further investigation indicated that CBZ-low significantly decreased the gamma-aminobutyric acid (GABA) level in the brain, while increased the serotonin (5-HT) level in the brain and cortisol level in plasma. Accordingly, the mRNA levels of genes in GABA (gad2, abat, gabrb2, gabrg2, gria1a and slc12a2) pathway and HPI (crha, actha, pc1 and pc2) axis were also altered. Despite the upregulation of tph2 was consistent with increased 5-HT level in the brain, significantly downregulated htr1aa and htr1b may indicate attenuated 5-HT potency. Although CBZ-high significantly reduced GABA level in the brain and increased cortisol level in plasma, the effects were dramatically alleviated than that of CBZ-low. Consistently, the expression of genes in HPI (crha, actha, pc1 and pc2) axis and GABA (gad2 and abat) pathway were also altered by CBZ-high, probably due to inconspicuous anxiety response of CBZ-high. Briefly, our data suggested that low concentration of CBZ disrupted zebrafish anxiety by interfering with neurotransmission and endocrine system, thereby bringing about adverse ecological consequences.

Intrauterine Injection of Umbilical Cord Mesenchymal Stem Cell Exosome Gel Significantly Improves the Pregnancy Rate in Thin Endometrium Rats.

Human umbilical cord mesenchymal stem cell (HUMSC)-exosome gel played a significant role in promoting thin endometrial receptivity and improving the pregnancy rate by inhibiting endometrial fibrosis and accelerating subendometrial microangiogenesis. High-quality HUMSC-exosome were obtained by pretreating HUMSC with transforming growth factor-ß1 (TGF-ß1). Exosome gel mixture has good biocompatibility and physical rheological properties, stabilizing the structure of exosomes and prolonging the action of exosomes in the uterine cavity. HUMSC or HUMSC-derived exosomes were used to treat rat model of thin endometrium. In animal experiments, four groups, including the HUMSC, HUMSC-exosome, model (negative control), and sham operation groups, were designed. The therapeutic effects were evaluated by the thickness of the endometrium, the number of glands, the subendometrial vessel density, the markers of endometrial receptivity, and the pregnancy rate. In an in vivo study, three groups, involving HUMSC-coculture, HUMSC-exosome, and the control, were explored. The proliferation and migration of the human endometrial stromal cells (HESCs) were further determined by cell scratch and 5-ethynyl-2'-deoxyuridine (EdU) assays. The protein expression of the TGF-ß1/smad2/3 signaling pathway was determined by Western blot. After treatment, the thickness of the endometrium, the number of glands, and the subendometrial microangiogenesis were obviously increased, and the level of inhibition of endometrial fibrosis, molecular markers of endometrial receptivity, and the pregnancy rate were also significantly improved. HUMSC-exosome and HUMSC significantly promoted the migration and proliferation of HESCs. And it was confirmed that HUMSC-exosome were superior to HUMSC in inhibiting HESCs fibrosis through TGF-ß1/smad2/3 signaling pathway at the protein expression level.

Complete mitochondrial genome of Acrossocheilus yunnanensis (Cypriniformes: Cyprinidae: Acrossocheilus) and its phylogenetic analysis.

Acrossocheilus yunnanensis is an endemic species in China. In this study, the complete mitochondrial genome of A. yunnanensis was determined. It was 16,587 bp in length, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a putative control region. Phylogenetic analysis showed that A. yunnanensis was clustered with A. monticola.

CT-guided percutaneous chemical ablation combined with radiofrequency ablation for hepatocellular carcinomas in high-risk locations: lobaplatin vs. ethanol.

To retrospectively compare the clinical efficacy and safety of CT-guided percutaneous injection of lobaplatin vs. ethanol for chemical ablation combined with radiofrequency ablation (RFA) in patients with hepatocellular carcinomas (HCCs) in high-risk locations. From January 2017 to June 2018, a total of 41 patients with HCCs in high-risk locations were enrolled and divided into two groups: percutaneous lobaplatin injection (PLI+RFA) group and percutaneous ethanol injection (PEI+RFA) group. The mixture of lobaplatin or ethanol was accurately injected into the high-risk part of the tumors, while RFA ablated the non-high-risk part. The efficacy and safety were compared between the two groups. 41 patients had 51 lesions in high-risk locations, including 24 cases with 30 lesions in PLI+RFA group and 17 cases with 21 lesions in PEI+RFA group. The complete ablation rate was 93.3% (28/30) in PLI+RFA group and 90.5% (19/21) in PEI+RFA group (P=1.000). The 2-year local tumor progression rate of PLI+RFA group and PEI+RFA group was 20.0% (6/30) and 19.0% (4/21), respectively (P=1.000). No significant differences were found in time to progression and overall survival between the two groups (P=0.501 and P=0.424, respectively). The incidence and severity of adverse events between the two groups were similar (P > 0.05). No severe complications were observed in both groups. Percutaneous lobaplatin injection combined with RFA in the treatment of HCC in high-risk locations may achieve the complete ablation rate similar to percutaneous ethanol injection combined with RFA, but further research is needed to confirm.

Climate Change Impact on Yield and Water Use of Rice-Wheat Rotation System in the Huang-Huai-Hai Plain, China.

Global climate change has had a significant impact on crop production and agricultural water use. Investigating different future climate scenarios and their possible impacts on crop production and water consumption is critical for proposing effective responses to climate change. In this study, based on daily downscaled climate data from 22 Global Climate Models (GCMs) provided by Coupled Model Intercomparison Project Phase 6 (CMIP6), we applied the well-validated Agricultural Production Systems sIMulator (APSIM) to simulate crop phenology, yield, and water use of the rice-wheat rotation at four representative stations (including Hefei and Shouxian stations in Anhui province and Kunshan and Xuzhou stations in Jiangsu province) across the Huang-Huai-Hai Plain, China during the 2041-2070 period (2050s) under four Shared Socioeconomic Pathways (i.e., SSP126, SSP245, SSP370, and SSP585). The results showed a significant increase in annual mean temperature (Temp) and solar radiation (Rad), and annual total precipitation (Prec) at four investigated stations, except Rad under SSP370. Climate change mainly leads to a consistent advance in wheat phenology, but inconsistent trends in rice phenology across four stations. Moreover, the reproductive growth period (RGP) of wheat was prolonged while that of rice was shorted at three of four stations. Both rice and wheat yields were negatively correlated with Temp, but positively correlated with Rad, Prec, and CO2 concentration ([CO2]). However, crop ET was positively correlated with Rad, but negatively correlated with [CO2], as elevated [CO2] decreased stomatal conductance. Moreover, the water use efficiency (WUE) of rice and wheat was negatively correlated with Temp, but positively correlated with [CO2]. Overall, our study indicated that the change in Temp, Rad, Prec, and [CO2] have different impacts on different crops and at different stations. Therefore, in the impact assessment for climate change, it is necessary to explore and analyze different crops in different regions. Additionally, our study helps to improve understanding of the impacts of climate change on crop production and water consumption and provides data support for the sustainable development of agriculture.

Sintilimab Combined with Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma in Second-Line Setting-A Multi-Center Observational Study.

Background: Patients with advanced intrahepatic cholangiocarcinoma (iCCA) have a poor prognosis and a substantial unmet clinical need. The study was aimed to investigate the efficacy and safety of sintilimab combined with lenvatinib for advanced iCCA in second-line setting. Methods: The patients at multiple centers, who progressed after the first-line chemotherapy or could not tolerate chemotherapy, were treated with the combination of sintilimab plus lenvatinib. The primary endpoint was time to progression (TTP), and the secondary endpoints included tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Prognostic factors were analyzed using Cox regression analysis. Results: A total of 41 patients with advanced iCCA were enrolled for this multi-center observational study. Under a median follow-up of 12.1 months, the median age was 59 years (range, 33-75 years). Sixteen patients died of disease progression, with a median TTP of 6.6 months (95% CI, 4.9-8.3). ORR and DCR were 46.3% and 70.3%, respectively. The patients with PD-L1 TPS ≥10% reported a significantly higher ORR compared to those with PD-L1 TPS <10%, 93.8% (15/16) vs. 16.0% (4/25), p<0.001. The median TTP was significantly improved in patients with PD-L1 TPS ≥10%, 16.9 months (95% CI, 7.5-26.3) vs. 4.1 months (95% CI, 1.8-6.4), p=0.001. Attaining treatment response predicts favorable TTP in a multivariate Cox model. Treatment-emergent adverse events occurred with 70.3% probability, and no treatment-related death had been reported. Conclusion: The combination of sintilimab plus lenvatinib is effective and well tolerated for advanced iCCA in the second-line setting. PD-L1 TPS expression may predict the efficacy of the combination therapy. Further investigation is warranted to investigate this combination regimen in advanced iCCA.

The Prognostic Role of Circulating FPR Before Operation in Patients with BCLC A-C Hepatocellular Carcinoma: A Retrospective Cohort Study.

Background: This research aimed to comprehensively assess the prognostic role of fibrinogen to prealbumin ratio (FPR) in BCLC A-C HCC patients treated by TACE and RFA. Methods: The research included 240 patients at stage BCLC A-C treated by TACE and RFA at Beijing Ditan Hospital of Capital Medical University from May 2011 to November 2018. Results: The results showed that the size of the tumor, vascular invasion, α-foetoprotein, cirrhosis, NLR, LMR, and PLR showed prognostic value in predicting 5-year OS. Besides, FPR (95% confidence interval: 1.006-1.013, hazard ratio: 1.009) was a prognostic factor for the prediction of 5-year OS in HCC. Conclusion: Our research indicated that FPR was a potential indicator for patients with BCLC A-C hepatocellular carcinoma after treatment of RFA and TACE.

Circular RNA ERBIN Promotes Proliferation of Hepatocellular Carcinoma via the miR-1263/CDK6 Axis.

Objectives: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and characterized by high aggressiveness and extremely poor prognosis. Increasing evidence has suggested that circular RNAs (circRNAs), which are highly stable, play crucial roles in the progression of multiple malignancies. However, the roles of circRNAs in HCC remain elusive. Materials and Methods: The expression patterns of circRNAs in HCC were identified by qRT-PCR. A series of functional experiments both in vivo and in vitro were used to determine the role of circERBIN in HCC proliferation. Bioinformatics and an RNA pulldown assay were used to identify potential downstream targets of circERBIN. Results: The expression of circERBIN was upregulated in HCC cell lines and tissues, which was predictive of a poor prognosis in HCC patients. Elevated circERBIN promoted G1/S transition of HCC cells, thus facilitating the proliferation and tumorigenesis of HCC cells. Mechanistic investigations revealed that circERBIN regulated HCC proliferation by acting as a sponge of miR-1263, which subsequently targeted cyclin dependent kinase 6 and controlled G1/S transition. Conclusion: Taken together, these results determined that circERBIN functions as an important epigenetic regulator in HCC development, highlighting that circERBIN is a promising target for treatment of HCC.