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AIM: To evaluate the changes of amplitude of accommodation(AA)and axial length(AL)undergoing overnight orthokeratology treatment. And to explore the mechanism of orthokeratology on controlling the development of myopia in pre-adolescent. METHODS: Prospective study, 215 pre-adolescent myopia aged 7-14 years old were enrolled in the study from May 2018 to August 2019. Every subject was measured for comprehensive eye examination. And according to the above measurements and the compliance of children and their parents, 113 patients who matched the inclusion criteria accepted treatment of orthokeratology(ortho-k group)and the other 102 subjects were selected to wear spectacle(spectacle group). During regular follow-up visits, AA was measured respectively at pre-wear, 1, 3, 6mo and 1a after orthokeratology. AL was measured at baseline and after 1a. The changes were evaluated and compared between the orthokeratology and spectacle group.RESULTS: After 1a follow-up, 100 eyes of 100 subjects in the ortho-k group completed the follow-up, and 13 eyes of 13 subjects were withdrawn from the study. In the spectacle group, 77 eyes of 77 subjects completed the study, and 25 eyes of 25 subjects were withdrawn. At baseline, the AA of myopia was 13.57±2.47D, the AA after 1, 3 and 6mo, 1a was significantly higher than before(all P

Cerasus conradinae is an important germplasm resource of wild cherry in China. In this work, sampling was expanded and genetic evidence was added for further study. The current and future potential populations were predicted by niche model. Based on three cpDNA sequences and one nrDNA sequence, and combined with the phylogeographic evolution of 12 populations of 244 individuals in C.conradinae, the temporal and spatial patterns of genetic variation in C.conradinae were investigated, and the effects of genetic drift and differentiation as well as natural environmental factors on the genetic variation and evolutionary distribution of C.conradinae were elucidated. Finally, morphological evidence combined with molecular evidence was used to discuss the species definition of population variation and differentiation. The results showed that Central China, East China and Southwest China were the core regions for the conservation and utilization of germplasm resources of C.conradinae. Support for variant Cerasus conradinae var. ruburm is established. The genetic diversity of C.conradinae was high (Hd = 0.830; Rd = 0.798). There was genetic variation among populations of C.conradinae, and genealogical geographic structure existed among the populations and three geographical groups, but the genetic differentiation coefficient at each level was low. The gene exchange was obvious in Southwest China, and the differentiation was obvious in Central China. The population and three geographic groups do not reject the expectation of expansion model. Two distinct lineages (three geographic groups) were identified from the population of C.conradinae: Central China+ East China lineage and East China+ (Central China+Southwest China) lineage, two lineages of 4.38Mya occurred in the early Pliocene based on geographical isolation. The southeastern part of Eastern China near Mount Wuyi was the most likely refuge for C.conradinae. The results provided a theoretical basis for the classification and identification of C.conradinae and the protection and utilization of germplasm resources.

Understanding large-scale patterns of biodiversity and their drivers remains significant in biogeography. Cherries species (Prunus subgenus Cerasus, Rosaceae) are economically and ecologically important in ecosystems and human agricultural activities. However, the mechanisms underlying patterns of species richness-environment relationship in Cerasus remain poorly understood. We collected and filtered worldwide specimen data to map the species richness of Cerasus at the global scale. The map of Cerasus species richness was created using 21043 reliable recorded specimens. The center of Cerasus diversity was determined using spatial cluster analysis. Stepwise regression analysis was carried out using five groups of 21 environmental variables and an integrated model was included to assess the impact of the overall environment. We calibrated each of the four integrated models and used them to predict the global Cerasus species richness and that of the other continents. Our results revealed that Cerasus species have two centers of diversity (the southwest of China and Honshu Island in Japan) with differing environmental variables influencing the distribution patterns of these two centers. In the southwest of China, hydrothermal conditions are the main driving factor while in Japan, habitat heterogeneity is the main driving factor. The relationship between the abundance of the Cerasus and the various groups of factors generally supported both the productivity and the habitat heterogeneity hypothesis. However, these hypotheses did not fully explain the Cerasus species richness pattern, indicating that other factors such as historical environment, topography, and human activities likely played a role in pattern formation. The high level of habitat heterogeneity and better hydrothermal conditions may have played an important role in the establishment of its globally consistent richness-climate relationship. Our results can provide valuable information for the classification, and conservation of Cerasus natural resources, as well as contribute to furthering our understanding of biogeography at a global scale.

IntroductionCentral pancreatectomy (CP) is a standard surgical procedure for benign and low-grade malignant pancreatic neoplasms in the body and neck of the pancreas. Higher incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) after CP than after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) has been reported, but no nomogram for prediction of CR-POPF after open CP has been previously established.MethodsPatients undergoing open CP for benign or low-grade malignant pancreatic neoplasms in the department of Hepatobiliary and Pancreatic (HBP) surgery of Shanghai Changhai Hospital affiliated to Naval Medical University between January 01, 2009 and December 31,2020 were enrolled. Pre-, intra- and post-operative parameters were analyzed retrospectively.ResultsA total of 194 patients, including 60 men and 134 women, were enrolled with median age of 52 years (21~85 years). 84 patients (43.3%) were overweight (BMI>23.0 Kg/m2) and 14 (7.2%) were obese (BMI>28.0 Kg/m2). Pathological diagnoses ranged from serous cystic neoplasm (32.5%), solid pseudopapillary neoplasm (22.2%), pancreatic neuroendocrine tumor (20.1%), intraductal papillary mucinous neoplasm (18.0%) to mucinous cystic neoplasm (5.2%). All patients had soft pancreatic texture. Main pancreatic duct diameters were ≤0.3cm for 158 patients (81.4%) and were ≥0.5cm in only 12 patients (6.2%). A stapler (57.7%) or hand-sewn closure (42.3%) were used to close the pancreatic remnant. The pancreatic anastomosis techniques used were duct to mucosa pancreaticojejunostomy (PJ)-interrupted suture (47.4%), duct to mucosa PJ-continuous suture (43.3%), duct to mucosa “HO” half-purse binding PJ (5.2%) and invaginating pancreaticogastrostomy (4.1%). Post-surgical incidences of CR-POPF of 45.9%, surgical site infection of 28.9%, postpancreatectomy hemorrhage of 7.7% and delayed gastric emptying of 2.1% were found. Obesity and pancreatic anastomosis technique were independent risk factors of CR-POPF, with a concordance index of 0.675 and an Area Under the Curve of 0.678.DiscussionThis novel nomogram constructed according to obesity and pancreatic anastomosis technique showed moderate predictive performance of CR-POPF after open CP.

Prenatal imaging phenotypes and genotypes were analyzed in 13 cases prenatally diagnosed with Joubert syndrome (JS), all of which underwent magnetic resonance imaging (MRI), ultrasound, and genetic testing. Prenatal MRI diagnosed 10 cases as JS with a typical molar tooth sign (MTS), while prenatal ultrasound diagnosed or suspiciously diagnosed 11 cases as JS with typical or mild MTS in 10 cases. Mutations in JS-related genes and other prenatal JS imaging phenotypes were identified in 10 cases, including OFD1 in two cases [cerebellar vermis (CV) absence, posterior fossa dilation, ventriculomegaly, polydactyly, malformations of cortical development (MCD), and persistent left superior vena cava], TMEM67 in two cases (CV absence, polydactyly, hyperechoic kidneys or polycystic kidneys, posterior fossa dilation, and ventriculomegaly), CC2D2A in two cases (CV absence, polydactyly, MCD, agenesis of the corpus callosum, encephalocele and hydrocephalus, ventriculomegaly, and posterior fossa dilation), RPGRIP1L in one case (CV absence), TCTN3 in one case (CV absence, polydactyly, MCD, and posterior fossa dilation), CEP290 in one case (CV absence and polycystic kidney), and NPHP1 in one case (CV absence). The prenatal diagnosis of JS presents a number of challenges, including the variants of unknown significance, the lack of functional assessment in prenatal imaging, unclear phenotype–genotype relationships in prenatal evaluation, and the incorrect identification of the JS hallmark, the MTS, in prenatal imaging, especially on ultrasound. Although combined MRI, ultrasound, and exome sequencing could help improve the prenatal diagnosis of JS, there still exist significant challenges.

Synonymous codon usage bias (SCUB) analysis is an effective method to explore species specificity, evolutionary relationships and mRNA translation, as well as to discover novel genes, which are important for understanding gene function and molecular phylogeny. Cherries (Prunus subg. Cerasus) are flowering plant germplasm resources for edible and ornamental purposes. In this study, we analyzed the codon usage patterns of the 36 chloroplast genomes to provide a scientific basis for elucidating the evolution of subg. Cerasus. The results showed that the average GC content was 0.377, the average GC3 was 0.298, and the average ENC value was 49.69. Neutral-plot analysis, ENC-plot analysis, and PR2-plot analysis all indicated that natural selection was the main factor of codon usage bias in subg. Cerasus, whereas correlation analysis showed that gene expression level and GC1 also affect the codon usage pattern. The codon usage pattern was consistent across 36 species, and 30 high-frequency codons were identified, with preference for A/T endings; there were 23 optimal codons, and only GAU was identified in all individuals; structural differences existed between the clustering tree based on RSCU values and the phylogenetic tree based on CDS, elucidating the importance of locus mutations and no-preference codons in phylogenetic reconstruction. This study describes for the first time the SCUB pattern and characterization of subg. Cerasus chloroplast genomes and provides a new insight to explore the phylogeny of this subgenus.

ObjectivesThis study aimed to examine the incidence of bifid pancreatic duct (BPD) in pancreaticoduodenectomy (PD) and clarify its impact on clinically relevant postoperative pancreatic fistula (CR-POPF).BackgroundUntil now, all the literature about BPD during PD are published as case reports, and the incidence of BPD in PD and its impact on CR-POPF remain unknown.ResultsA total of 438 consecutive PDs were divided into two groups: the former year group and the latter year group. The former year group included 215 consecutive PDs, while the latter year group included 223. In the latter year group, we found 16 BPDs during PD (O-BPD); the incidence of O-BPD is 7.17%. Of them, there were eight patients who had BPD in the preoperative imaging (I-BPD). All the I-BPDs are O-BPDs; which means that 50% of O-BPDs were a single pancreatic duct in the preoperative imaging (I-SPD). There were 17 I-BPDs in the 438 consecutive PDs; the incidence of I-BPD is 3.88%. In the former year group, the rate of severe complications of I-BPD and I-SPD is 77.78% and 27.18%, respectively (p = 0.003); the rate of CR-POPF of I-BPD is higher than I-SPD, 55.56% vs. 27.18%, but there were no statistically significant differences. In the latter year group, the rate of severe complications of O-BPD and O-SPD is 50% and 18.36%, and the rate of CR-POPF of O-BPD and O-SPD is 37.5% and 22.22%, respectively; both of them have statistically significant differences, and the p-value is 0.003 and 0.006, respectively. In the subgroup analysis, both the rate of severe complications and the rate of CR-POPF of I-BPD were higher than O-BPD, 77.78% vs. 50%, and 55.56% vs. 37.5%, but there were no statistically significant differences in both of them; the p-value is 0.174 and 0.434, respectively. Univariate and multivariate analyses showed that BPD was an independent risk factor of CR-POPF.ConclusionsThe incidence of O-BPD in PD is 7.17%, 50% of O-BPDs were I-SPD, and the incidence of I-BPD is 3.88%. BPD is an independent risk factor of CR-POPF. The suture closure method may be a simple, safe, and effective method in dealing with BPD in PD.

Introduction Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin's lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated. Patients and methods Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry. Results We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan-Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time. Discussion These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.

Cerasus serrulata (Rosaceae) is an important flowering cherry resource which is valuable for developing new cultivars of flowering cherries. It is broadly distributed and possesses abundant variations. In this study, phylogeographic analysis was conducted to reveal the evolutionary history to better understand the genetic diversity and genetic structure of C. serrulata so as to provide more accurate molecular insights into better conservation and utilization of the germplasm resources. A total of 327 individuals from 18 wild populations were collected. Three chloroplast DNA (cpDNA) fragments (matK, trnD‐E, and trnS‐G) and the nuclear internal transcribed spacer (ITS) were utilized. The results showed a high genetic diversity at both species level and population level of C. serrulata. High genetic differentiation and the existence of the phylogeographic structure were detected. No significant expansion events were discovered. Two geographic lineages were inferred. One was confined to the Qinling Mountains and the Taihang Mountains. The other was from the Wuling Mountains to the Jiangnan Hilly Regions and then went northeast to the coast of Asia. In addition, some taxonomic treatments of the C. serrulata complex are discussed and reconsidered. Conservation and utilization strategies of wild C. serrulata germplasm resources were recommended., Cerasus serrulata (Rosaceae) distributes in the main subtropical and temperate China as almost the most widely distributed cherry. It shows variable morphological traits, especially in ornamental traits, making it a significantly important cherry resource. We covered the major distributions and collected 18 populations to study the phylogeography of C. serrulata using three cpDNA fragments (matK, trnD‐E, trnS‐G) and the nuclear ITS to see its spatiotemporal evolutionary pattern to bring insights into evolutionary history of the genus and of plants within this region. We revealed the genetic structure of C. serrulata which also brought taxonomic proofs to the controversial treatments of the C. serrulata complex, and finally found two geographical lineages and inferred the evolutionary routines of C. serrulata.

Subtropical forest in China has received much attention due to its complex geologic environment and bioclimatic heterogeneity. There have been very few studies addressing which climatic factors have shaped both distribution patterns and niche differentiation of species from this region. It also remains unclear whether phylogenetic niche conservatism retains in plant species from this biodiversity-rich subtropical region in China. In this study, we used geographic occurrence records and bioclimatic factors of Prunus dielsiana (Rosaceae), a wild cherry species, combined with the classical ENM-based DIVA-GIS software to access contemporary distribution and richness patterns of its natural populations. The current distribution of P. dielsiana occupied a relatively wide range but exhibited an uneven pattern eastward in general, and the core distribution zone of its populations are projected to concentrate in the Wushan and Wuling Mountain ranges of western China. Hydrothermic variables, particularly the Temperature Seasonality (bio4) are screened out quantitatively to be the most influential factors that have shaped the current geographical patterns of P. dielsiana. By comparison with other sympatric families, climatic niche at regional scale showed a pattern of phylogenetic niche conservatism within cherry species of Rosaceae. The effect of habitat filtering from altitude is more significant than those of longitude and latitude. We conclude that habitat filtering dominated by limiting hydrothermic factors is the primary driving process of the diversity pattern of P. dielsiana in subtropical China.

Our results from iTRAQ-based proteomics extend the understanding of the mechanisms employed by AMF to defend against drought stress in blueberry. Arbuscular mycorrhizal fungi (AMF) can substantially contribute to plant drought tolerance. In this work, south highbush blueberry (Vaccinium corymbosum) ‘O’Neal’ cultivated with or without Funneliformis mosseae inoculation under well-watered or drought-stressed conditions were evaluated through an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics approach. In total, 3078 proteins and 501 differentially abundant proteins (DAPs) were identified, including 127, 30, 236, and 108 DAPs in drought-stressed plants vs well-watered, drought-stressed plants with AMF inoculation vs well-watered plants with AMF inoculation, AMF-inoculated well-watered plants vs non-inoculated well-watered plants, and AMF-inoculated plants under drought stress vs non-inoculated plants under drought stress paired comparisons, respectively. Relative to non-inoculated plants, AMF-inoculated plants under drought stress maintained a greater abundance of DAPs involved in amino acid metabolism, antioxidant system, signal transduction, and photosynthesis including carbon fixation in photosynthetic organisms, porphyrin and chlorophyll metabolism, and carotenoid biosynthesis. Physiological analyses revealed that AMF-inoculated plants exhibited a greater photosynthetic capacity than non-inoculated plants under drought stress, mainly through non-stomatal factors such as enhancements of the efficiency of excitation energy capture by chloroplasts and the photochemical capacity of photosystems. Thus, the findings could explain the AMF-induced physiological effects associated with drought tolerance. Studies on the proteomic responses specific to AMF in drought-stressed plants will help to clarify how mycorrhization elicits improved plant growth and stress tolerance responses.

Background The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL). Methods The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing. Results We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis. Conclusion Our results unveil the mutation spectrum of ENKTL patients’ plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients. Trial registration This study is registered with chictr.org (ChiCTR1800014813, registered 7 February, 2018-Retrospectively registered).

Osmanthus (Oleaceae) is considered one of the most confusing genera with regards to circumscription and phylogenetic placement of taxa within the subtribe Oleinae of Oleaceae, with controversies mainly focused on the attribution of section Leiolea. In the present study, we analyzed 71 samples that represent the broad taxonomic, biogeographic, and morphological patterns in the subtribe Oleinae. Based on concatenation of four plastid genes (trnL-F, trnT-L, trnS-G, and matK) and comparison with the ITS region, Bayesian Inference, Maximum Likelihood and Maximum Parsimony phylogenies were inferred. Morphological character traits and geographical distributions of taxa were also studied. These results provide strong support for the segregation of the Leiolea clade (Osmanthus marginatus, O. matsumuranus and O. minor) of sect. Leiolea from Osmanthus. Therefore, the Leiolea clade is instated as the new genus Chengiodendron, with a taxonomic treatment provided. This study provides a clearer understanding of the phylogenetic relationships of genera in the subtribe Oleinae.

BACKGROUND: The mechanisms involved in the malignant progression of lung adenocarcinoma (LUAD) are still inconclusive. Fibrinogen-like protein 1 (FGL1) and LAG3 are a pair of immune checkpoints that create an inhibitory immune microenvironment in tumors. However, other roles of FGL1 in LUAD have not been extensively studied. Our study aims to explore the role of FGL1 in the malignant progression of LUAD and to provide new therapeutic targets and strategies for LUAD treatment. METHODS: Differential gene expression of FGL1 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, UALCAN, and Gene Expression Omnibus (GEO) databases. A pan-cancer analysis was conducted using the Oncomine, TIMER, and UALCAN databases. A total of 140 tumor tissues and paired normal tissues were collected, IHC and immunofluorescence staining were used to explore the expression of FGL1. GeneMANIA database and STRING database were used to analyze gene-gene interaction and protein-protein interaction, respectively. A mutation analysis was conducted using the cBioPortal database, and an immune infiltration analysis was conducted using the TIMER database. A survival analysis was carried out using the GEPIA and PrognoScan database. The knockdown of FGL1 was confirmed by western blot (WB) and immunofluorescence staining. Cell proliferation was tested by cell cycle analysis and real-time cell analysis. RNA sequencing (RNA-seq) was used to explore the differential genes of FGL1 knockdown in LUAD cells. RESULTS: Multiple databases showed that FGL1 was highly expressed in LUAD. The results of IHC indicated that FGL1 was highly expressed in the cytoplasm of LUAD cells. FGL1 was negatively associated with immune infiltration in LUAD. The main mutation of FGL1 is deep deletion, the altered group and high expression group indicated poor prognosis. The downregulation of FGL1 lead to a significantly decreased percentage of PC9 cells in S phase, but had little effect on the proliferation of Jurkat T cells. RNA-seq and GSEA analysis indicated that the differential genes were mainly enriched in MYC-target genes, which suggested that the downregulation of FGL1 inhibited cell proliferation by regulating MYC-target genes. CONCLUSIONS: FGL1 exerts in LUAD proliferation in addition to immune regulation. The downregulation of FGL1 inhibits the proliferation of LUAD cells by regulating MYC-target genes. Thus, FGL1 may be a novel therapeutic target in LUAD.