A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Ethanol exposure exacerbates 4-nitroquinoline-1-oxide induced esophageal carcinogenesis and induces invasive carcinoma with muscularis propria infiltration in a mouse model.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. Most ESCC patients are diagnosed at an advanced stage; however, current research on in vivo animal models accurately reflecting their clinical presentation is lacking. Alcohol consumption is a major risk factor for ESCC and has been used in several disease models for disease induction. In this study, we used 4-nitroquinoline-1-oxide in combination with ethanol to induce an in vivo ESCC mouse model. Esophageal tissues were stained with hematoxylin and eosin for histopathological examination and lesion scoring. In cellular experiments, cell adhesion and migration invasion ability were observed using phalloidin staining, cell scratch and transwell assays, respectively, and the expression of epithelial-mesenchymal transition-related markers was detected using quantitative reverse transcription polymerase chain reaction and western blotting. The results showed that ethanol-exposed mice lost more weight and had an increased number of esophageal nodules. Histological examination revealed that the lesion scores of the ethanol-exposed esophageal samples were significantly higher than those of the unexposed esophageal samples. Furthermore, ethanol-exposed esophageal cancer samples had more severe lesions with infiltration of tumor cells into the muscularis propria. In vitro cellular experiments showed that ethanol exposure induced cytoskeletal microfilament formation, promoted cell migration invasion elevated the expression of N-cadherin and Snail, and decreased the expression of E-cadherin. In conclusion, ethanol exposure exacerbates ESCC, promotes tumor cell infiltration into the muscularis propria, and could be an effective agent for establishing innovative models of invasive carcinoma.

Genomic formation of Tibeto-Burman speaking populations in Guizhou, Southwest China.

Sino-Tibetan is the most prominent language family in East Asia. Previous genetic studies mainly focused on the Tibetan and Han Chinese populations. However, due to the sparse sampling, the genetic structure and admixture history of Tibeto-Burman-speaking populations in the low-altitude region of Southwest China still need to be clarified. We collected DNA from 157 individuals from four Tibeto-Burman-speaking groups from the Guizhou province in Southwest China. We genotyped the samples at about 700,000 genome-wide single nucleotide polymorphisms. Our results indicate that the genetic variation of the four Tibeto-Burman-speaking groups in Guizhou is at the intermediate position in the modern Tibetan-Tai-Kadai/Austronesian genetic cline. This suggests that the formation of Tibetan-Burman groups involved a large-scale gene flow from lowland southern Chinese. The southern ancestry could be further modelled as deriving from Vietnam's Late Neolithic-related inland Southeast Asia agricultural populations and Taiwan's Iron Age-related coastal rice-farming populations. Compared to the Tibeto-Burman speakers in the Tibetan-Yi Corridor reported previously, the Tibeto-Burman groups in the Guizhou region received additional gene flow from the southeast coastal area of China. We show a difference between the genetic profiles of the Tibeto-Burman speakers of the Tibetan-Yi Corridor and the Guizhou province. Vast mountain ranges and rivers in Southwest China may have decelerated the westward expansion of the southeast coastal East Asians. Our results demonstrate the complex genetic profile in the Guizhou region in Southwest China and support the multiple waves of human migration in the southern area of East Asia.

Multi-Carrier Generation in Organic-Passivated Black Silicon Solar Cells with Industrially Feasible Processes.

The innate inverse Auger effect within bulk silicon can result in multiple carrier generation. Observation of this effect is reliant upon low high-energy photon reflectance and high-quality surface passivation. In the photovoltaics industry, metal-assisted chemical etching (MACE) to afford black silicon (b-Si) can provide a low high-energy photon reflectance. However, an industrially feasible and cheaper technology to conformally passivate the outer-shell defects of these nanowires is currently lacking. Here, a technology is introduced to infiltrate black silicon nanopores with a simple and vacuum-free organic passivation layer that affords millisecond-level minority carrier lifetimes and matches perfectly with existing solution-based processing of the MACE black silicon. Advancements such as the demonstration of an excellent passivation effect whilst also being low reflectance provide a new technological route for inverse Auger multiple carrier generation and an industrially feasible technical scheme for the development of the MACE b-Si solar cells.

Circ_0001589/miR-1248/HMGB1 axis enhances EMT-mediated metastasis and cisplatin resistance in cervical cancer.

Cervical cancer is the fourth most common malignant tumors in female worldwide. Cirular RNAs (circRNA) represent a new class of regulatory RNA and play a pivotal role in the carcinogenesis and development of tumors. However, their functions have not been fully elucidated in cervical cancer. In this study, we identified an upregulated circRNA, circ_0001589, both in fresh clinical samples and tissue microarray of cervical cancer. Transwell assay and cell apoptosis assay by flow cytometry demonstrated circ_0001589 promotes epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion, and enhanced cisplatin resistance in vitro. In addition, in nude mice model, circ_0001589 increased the number of lung metastases and recovered xenograft growth from cisplatin treatment in vivo. Mechanistically, RNA pull-down assay, RNA immunoprecipitation, and dual-luciferase reporter assay disclosed that circ_0001589 function as an competing endogenous RNA to sponge miR-1248, which directly target the 3' untranslated region of high mobility group box-B1 (HMGB1). Thereby, circ_0001589 upregulated HMGB1 protein expression and accelerate cervical cancer progression. The rescue experiments also revealed that miR-1248 overexpression or HMGB1 knockdown partially reversed the regulatory functions of circ_0001589 on cell migration, invasion, and cisplatin resistance. In summary, our findings suggest the upregulation of circ_0001589 promoted EMT-mediated cell migration and invasion, and enhanced cisplatin resistance via regulating miR-1248/HMGB1 axis in cervical cancer. These results provided new evidence for understanding the carcinogenesis mechanism and finding new therapeutic target for cervical cancer.

Potentiated effects of lactate receptor GPR81 on immune microenvironment in breast cancer.

G protein-coupled receptor (GPR81), as lactate receptor, is an upstart in immune regulation, however, its mechanisms involved in tumor escape have not been fully elucidated. In this study, we explored the effects of GPR81 activation on triple-negative breast cancer (TNBC) cells and macrophages. The expression and relationship with immune infiltration of GPR81 were analyzed with TCGA database. Checkpoints and cytokines were evaluated with flow cytometry or ELISA. The TCGA-based data showed a marked decrease of GPR81 in breast cancer (BRCA) compared with normal breast, especially in the basal-like subtype. In normal mammary tissues, GPR81 had negative correlation with various immune checkpoints, nevertheless, this trend weakened accompanied with the reduction of GPR81. GPR81 stimulation had a significantly inhibitory influence on PD-L1 exposure in BT-549 and MDA-MB-231 cell lines, but not in MDA-MB-453 cell line. The pretreatment of siGPR81 to knockdown GPR81 expression resulted in a remitting of PD-L1 reduction when MDA-MB-231 cells were treated with GPR81 agonist 1. However, little effect of GPR81 activation was observed on the expression of PD-L1 on phorbol-12-myristate-13-acetate (PMA)-induced THP-1 cells. Furthermore, GPR81 agonist 1 exerted no significant impact on the secretion of cytokines in THP-1 cells. In general, it is suggested that GPR81 may facilitate immune monitoring via the reduction of PD-L1 in TNBC with glycolytic phenotype. Our results not only provide a novel insight into the effects of GPR81 on immune evasion but a potential therapy targeting GPR81 in BRCA.

Dietary Supplementation with Lauric Acid Improves Aerobic Endurance in Sedentary Mice via Enhancing Fat Mobilization and Glyconeogenesis.

BACKGROUND: Lauric acid (LA), a major, natural, medium-chain fatty acid, is considered an efficient energy substrate for intense exercise and in patients with long-chain fatty acid ß-oxidation disorders. However, few studies have focused on the role of LA in exercise performance and related glucolipid metabolism in vivo. OBJECTIVES: We aimed to investigate the effect of dietary supplementation with LA on exercise performance and related metabolic mechanisms. METHODS: Male C57BL/6N mice (14 wk old) were fed a basal diet or a diet containing 1% LA, and a series of exercise tests, including a high-speed treadmill test, aerobic endurance exercises, a 4-limb hanging test, and acute aerobic exercises, were performed. RESULTS: Dietary supplementation with 1.0% LA accelerated the recovery from fatigue after explosive exercise (P < 0.05) and improved aerobic endurance and muscle strength in sedentary mice (P = 0.039). Lauric acid intake not only changed muscle fatty acid profiles, including increases in C12:0 and n-6/n-3 PUFAs (P < 0.001) and reductions in C18:0, C20:4n-6, C22:6n-3, and n-3 PUFAs (P < 0.05) but also enhanced fat mobilization from adipose tissue and fatty acid oxidation in the liver, at least partly via the AMP-activated protein kinase-acetyl CoA carboxylase pathway (P < 0.05). Likewise, LA supplementation promoted liver glyconeogenesis and conserved muscular glycogen during acute aerobic exercise (P < 0.05), which was accompanied by an increase in the mitochondrial DNA copy number and Krebs cycle activity in skeletal muscle (P < 0.05). CONCLUSIONS: Dietary supplemental LA serves as an efficient energy substrate for sedentary mice to improve aerobic exercise endurance and muscle strength through regulation of glucolipid metabolism. These findings imply that LA supplementation might be a promising nutritional strategy to improve aerobic exercise performance in sedentary people.

Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment.

BACKGROUND: Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis. METHODS: Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse. RESULTS: Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical-striatal-thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse. CONCLUSION: MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.

Improving spatial resolution and diagnostic confidence with thinner slice and deep learning image reconstruction in contrast-enhanced abdominal CT.

OBJECTIVE: To evaluate image quality and diagnostic confidence improvement using a thin slice and a deep learning image reconstruction (DLIR) in contrast-enhanced abdominal CT. METHODS: Forty patients with hepatic lesions in enhanced abdominal CT were retrospectively analyzed. Images in the portal phase were reconstructed at 5 mm and 1.25 mm slice thickness using the 50% adaptive statistical iterative reconstruction (ASIR-V) (ASIR-V50%) and at 1.25 mm using DLIR at medium (DLIR-M) and high (DLIR-H) settings. CT number and standard deviation of the hepatic parenchyma, spleen, portal vein, and subcutaneous fat were measured, and contrast-to-noise ratio (CNR) was calculated. Edge-rise-slope (ERS) was measured on the portal vein to reflect spatial resolution and the CT number skewness on liver parenchyma was calculated to reflect image texture. Two radiologists blindly assessed the overall image quality including subjective noise, image contrast, visibility of small structures using a 5-point scale, and object sharpness and lesion contour using a 4-point scale. RESULTS: For the 1.25-mm images, DLIR significantly reduced image noise, improved CNR and overall subjective image quality compared to ASIR-V50%. Compared to the 5-mm ASIR-V50% images, DLIR images had significantly higher scores in the visibility and contour for small structures and lesions; as well as significantly higher ERS and lower CT number skewness. At a quarter of the signal strength, the 1.25-mm DLIR-H images had a similar subjective noise score as the 5-mm ASIR-V50% images. CONCLUSION: DLIR significantly reduces image noise and maintains a more natural image texture; image spatial resolution and diagnostic confidence can be improved using thin slice images and DLIR in abdominal CT. KEY POINTS: • DLIR further reduces image noise compared with ASIR-V while maintaining favorable image texture. • In abdominal CT, thinner slice images improve image spatial resolution and small object visualization but suffer from higher image noise. • Thinner slice images combined with DLIR in abdominal CT significantly suppress image noise for detecting low-density lesions while significantly improving image spatial resolution and overall image quality.

Clinical Observation of Macular Superficial Capillary Plexus and Ganglion Cell Complex in Patients with Parkinson's Disease.

INTRODUCTION: We investigated macular superficial capillary plexus (SCP) density and the thicknesses of the ganglion cell complex (GCC) in patients with Parkinson's disease (PD) and correlated them. We also observed the correlations between SCP density and clinical parameters of PD patients. The retina might be a novel biomarker of PD and will be useful in the future for the early diagnosis of PD and detecting disease progression. METHODS: Seventy-four participants (38 patients with PD and 36 healthy controls) were recruited at the Affiliated Hospital of Xuzhou Medical University between January 2022 and June 2022 in this study. The macular SCP densities was measured by optical coherence tomography angiography (OCTA), and the GCC thickness was measured by optical coherence tomography (OCT). The parameters were compared between PD patients and healthy controls. The correlation between SCP and clinical parameters was tested. RESULTS: Compared with the control group, PD patients showed reduced SCP densities in all areas of the macular region (parafovea-temporal: t = 3.053, p = 0.003; parafovea-superior: t = 3.680, p = 0.001; parafovea-nasal: t = 4.643, p < 0.001; parafovea-inferior: t = 2.254, p = 0.027; perifovea-temporal: t = 3.798, p < 0.001; perifovea-superior: t = 3.014, p = 0.004; perifovea-nasal: t = 2.948, p = 0.004; perifovea-inferior: t = 3.337, p = 0.021). The average GCC thickness in the PD patients was significantly reduced (t = 2.365, p = 0.021). There were positive correlations between the average GCC thickness and the SCP densities in most of the areas of the macular regions in PD patients (parafovea-temporal: r = 0.325, p = 0.005; parafovea-superior: r = 0.295, p = 0.011; parafovea-nasal: r = 0.335, p = 0.003; perifovea-superior: r = 0.362, p = 0.002; perifovea-nasal: r = 0.290, p = 0.012; perifovea-inferior: r = 0.333, p = 0.004). We found significant correlations between SCP densities and Hoehn and Yahr (H and Y) scales, UPDRS III scores, and MMSE scores. No significant correlation was observed between SCP density and PD disease duration (all p > 0.05). CONCLUSIONS: We demonstrated that the macular SCP density was decreased, and the average GCC thickness was reduced in PD patients. The correlation between SCP density damage and GCC thinning also suggested that the retinal microvascular damage may be associated with retinal structural degeneration in PD patients. OCTA and OCT may be considered objective biomarkers for detecting microvascular impairment and neuronal damage in the early stages of PD in the future.

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial-mesenchymal transition and stemness through Wnt/ß-catenin signaling.

Endometrial cancer (EC) is one of the most common cancers among women, while the incidence of EC is rising. Many studies have found that Kinesin family member 15 (KIF15) is highly expressed in a series of cancers, but the role of KIF15 in EC is unclear. We detected the expression level of KIF15 in a microarray of EC tissues by immunohistochemical staining (IHC), and analyzed the correlation between the expression level of KIF15 and the pathological characteristics of patients. After inhibit the expression of KIF15 in EC cells with lentivirus, cell proliferation and apoptosis were detected respectively by CCK8 assay, flow cytometry and tunnel assay. Transwell assay and wound healing assay were used to examine the migration ability and invasion ability of EC cells. Spheroid formation assay was used to evaluate cell self-renewal ability. In vivo tumor xenograft model was used for validation. The expressions of epithelial-mesenchymal transition, cancer stem cells, and Wnt/ß-catenin signaling molecules were detected by Western blotting. The results showed that the expression of KIF15 in EC tissues was higher than that in normal endometrial tissues, while the expression level of KIF15 in EC was positively correlated with the pathological grade of the tumor. The down-regulation of KIF15 reduced the proliferation, colony formation, invasion, migration and self-renewal ability of EC cells, while promoted cell apoptosis. Knockdown of KIF15 inactivates the Wnt/ß-catenin signaling of EC cells, inhibitors of Wnt signaling can counteract the enhanced self-renewal ability caused by KIF15 overexpression. Therefore, KIF15 may be a new potential target for diagnosis and treatment of EC.

First-principles study of polymer-passivated silicon nanowire outer-shell defects.

Highly effective defect passivation schemes are very important for the improvement of Si nanowire (SiNW) performances, because large numbers of outer-shell-defect states are caused by the high surface-to-volume ratios of nanowires. In this work, a polymer that can be fabricated by a simple, vacuum-free method at low temperatures, Nafion, was studied for the SiNW outer-shell defect passivation using first-principles calculations. Based on adsorption energy calculations, it was found that the Nafion molecule could firmly adsorb on the surfaces of SiNWs along the 〈112〉 direction. The Nafion-passivated SiNW outer-shell exhibited high stability to a chemical environment. Herein, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were confined to the center of the SiNW due to being wrapped by the Nafion. The Nafion-passivated SiNWs exhibited an equivalent quantum confinement effect and a larger absorption coefficient compared with the H-passivated SiNWs. This work demonstrated a passivation strategy of SiNW shell defects using functional groups.

Unveiling the roles of halogen ions in the surface passivation of CsPbI3 perovskite solar cells.

Halide ion passivation is an effective way to improve the stability and the power conversion efficiency (PCE) of perovskite solar cells. In this work, the passivation mechanism of the surface iodine vacancies of inorganic perovskite CsPbI3 films by halogen ions (F-, Cl-, and Br-) has been studied using the first-principles method. Due to its high electronegativity, the F ion withdraws electron density out of its neighboring atoms, readily forms ionic bonds with Pb atoms and has a coupling effect with the nearest neighbor Cs atoms, which can alleviate the generation of cation vacancy and ion migration to locally stabilize the structure of the perovskite. The fluorinated CsPbI3 (001) surface has a lower surface energy, which improves the grain growth of perovskite films. Different from F-, the passivation via Cl- or Br- ions can effectively prevent the charge accumulation on the film surface, reduce the exciton binding energy of CsPbI3, and eliminate the loss of optical absorption intensity in the visible light range caused by iodine vacancies. These results provide a deep understanding about surface passivation by halogen ions for perovskite solar cells.

Image quality improvement in low-dose chest CT with deep learning image reconstruction.

OBJECTIVES: To investigate the clinical utility of deep learning image reconstruction (DLIR) for improving image quality in low-dose chest CT in comparison with 40% adaptive statistical iterative reconstruction-Veo (ASiR-V40%) algorithm. METHODS: This retrospective study included 86 patients who underwent low-dose CT for lung cancer screening. Images were reconstructed with ASiR-V40% and DLIR at low (DLIR-L), medium (DLIR-M), and high (DLIR-H) levels. CT value and standard deviation of lung tissue, erector spinae muscles, aorta, and fat were measured and compared across the four reconstructions. Subjective image quality was evaluated by two blind readers from three aspects: image noise, artifact, and visualization of small structures. RESULTS: The effective dose was 1.03 ± 0.36 mSv. There was no significant difference in CT values of erector spinae muscles and aorta, whereas the maximum difference for lung tissue and fat was less than 5 HU among the four reconstructions. Compared with ASiR-V40%, the DLIR-L, DLIR-M, and DLIR-H reconstructions reduced the noise in aorta by 11.44%, 33.03%, and 56.1%, respectively, and had significantly higher subjective quality scores in image artifacts (all p < 0.001). ASiR-V40%, DLIR-L, and DLIR-M had equivalent score in visualizing small structures (all p > 0.05), whereas DLIR-H had slightly lower score. CONCLUSIONS: Compared with ASiR-V40%, DLIR significantly reduces image noise in low-dose chest CT. DLIR strength is important and should be adjusted for different diagnostic needs in clinical application.

Has COVID-19 accelerated the E-commerce of agricultural products? Evidence from sales data of E-stores in China.

We investigated the operation of e-stores specializing in food and agricultural products before and after the occurrence of COVID-19. A difference-in-difference (DID) method was employed to estimate the relationship between COVID-19 and the online sales of agricultural products using data from 164,002 food and agricultural product e-commerce stores (in short, e-stores) of two major Chinese e-commerce platforms in 120 prefectural-level or above cities. The results demonstrated that while COVID-19 and its control measures were associated with a substantial growth in the monthly sales of food and agricultural product e-stores, the growth varies considerably across store scales and with the type of food and agricultural product in which an e-store is specialized. Micro stores experienced much larger growth and played a more important role in maintaining the resilience of the supply chain of food and agricultural products than larger-scale stores; stores selling more essential food items experienced larger growth than those selling leisure food items. A mechanism analysis further revealed that the growth of online sales of agricultural products was mainly driven by changes in consumers' food purchase behaviors from offline channels to online channels (i.e., an increase in the number of online customer orders and price per online order) starting with the onset of COVID-19. The results of this paper underscore the importance of e-commerce in maintaining the resilience of the agri-food supply chain and call for public support of the development of micro- and small-scale e-stores to meet consumers' increasing demand for food supply from those types of stores during the pandemic period.

New insights into the fine-scale history of western-eastern admixture of the northwestern Chinese population in the Hexi Corridor via genome-wide genetic legacy.

Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.

Differentiating total from subtotal arterial occlusion in lower extremities by using reverse attenuation gradient sign in CT angiography.

OBJECTIVES: To investigate the use of reverse attenuation gradient sign (RAGS) in CT angiography (CTA) to differentiate total from subtotal occlusion in lower extremities which poses different challenges for the procedure and carries different prognoses. METHODS: Eighty patients with 91 lesions in the lower extremities were divided into total occlusion (TO) group and subtotal occlusion (SO) group confirmed by digital subtraction angiography. The CT numbers of vascular lumen at the end of lesion (proximal, P) and at the first entrance (distal, D) of the lateral branch were measured and their difference (CT(PD) = CT(P) - CT(D)) of each lesion was calculated. The CT number gradient (G(DP) = 2 * CT(PD)/[CT(P) + CT(D)]) was calculated by dividing the CT number difference by the average CT number of the two points. The existence of RAGS where the CT number at the distal point is higher than that at the proximal point (CT(PD) and G(PD) < 0) was determined and the diagnostic efficacy of using RAGS in CTA for differentiating total from subtotal occlusive lesions in lower extremities was calculated. RESULTS: The SO group had higher CT numbers than the TO group (p < 0.001). More importantly, the SO group had positive CT number gradient (G(PD) > 0), while the gradient was negative (G(PD) < 0) in the TO group. The specificity and sensitivity of using RAGS (G(PD) < 0) in images for diagnosing TO of lower extremity were 97.6% and 92.0%, respectively, and 87.8% and 88.0% using the standard CTA images. CONCLUSION: The use of RAGS in CTA images has high diagnostic accuracy to differentiate TO from SO in lower extremities. KEY POINTS: • Total occlusions often exhibit higher CT number at distal point than at proximal point to the occlusion. • The reverse attenuation gradient sign (RAGS) may be determined using the CT number measurements between the proximal and distal points after occlusion. • RAGS can be used to improve the diagnostic efficiency in CTA to differentiate between total and subtotal occlusions of lower extremity arteries.

Stereospecific Synthesis of Cyclic Sulfite Esters with Sulfur-Centered Chirality via Diastereoselective Strategy and Intramolecular H-Bonding Assistance.

Stereospecific synthesis of several cyclic sulfite esters containing three stereogenic centers from enantiopure 1,1,4,4-tetraarylbutanetetraols was achieved. Chiral sulfur centers were constructed stereospecifically via a diastereoselective reaction with the assistance of an intramolecular H-bonding interaction. The absolute configuration of the S atom was elucidated by using the corresponding single-crystal X-ray diffraction analysis of the synthesized monochloride cyclic sulfite esters. Furthermore, a crystallographic evidence of the specific intramolecular C(sp3)-H···CAr weak H-bondings was presented, and its dramatic effect on the 1H NMR spectral properties was revealed. This intriguing behavior was unambiguously rationalized by different shielding effects of the neighboring phenyl rings. Additionally, the theoretical results obtained on the basis of MP2 calculations fully supported the existence of intramolecular hydrogen bonding interactions being responsible for the observed unique chemical and spectral properties.

Comparison of survival outcomes between laparoscopic surgery and abdominal surgery for radical hysterectomy as primary treatment in patients with stage IB2/IIA2 cervical cancer.

OBJECTIVE: To investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for the treatment of stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. METHODS: We conducted a multicenter, retrospective, case-matching study. The differences in overall survival (OS) and disease-free survival (DFS) between the LRH and ARH were compared under the conditions of real-world study and case-control matching (1:1 matching). RESULTS: There was no significant difference in the outcomes of LRH (n = 580) and ARH (n = 1653) in 5-year OS and DFS (OS: 80.6% vs. 86.1%, p = 0.421; DFS: 78.6% vs. 80.7%, p = 0.376). After 1:1 matching, there was no difference in 5-year OS and DFS between LRH (n = 554) and ARH (n = 554) (OS: 80.4% vs. 84.5%, p = 0.993; DFS: 79.0% vs. 78.8%, p = 0.695). Before and after matching, the surgical approach was not an independent risk factor for 5-year OS and DFS, and postoperative adjuvant therapy affected patient prognosis. Further subgroup analysis suggested that there was no difference in LRH (n = 313) and ARH (n = 1092) in 5-year OS or DFS in patients who underwent standard postoperative adjuvant therapy (OS: 83.0% vs. 87.7%, p = 0.992; DFS: 79.0% vs. 82.5%, p = 0.323). After 1:1 pairing, the 5-year OS and DFS in LRH (n = 295) and ARH (n = 295) showed no difference. Before and after matching, the surgical approach was not an independent risk factor affecting the 5-year OS and DFS. CONCLUSIONS: There was no difference in the oncological outcomes between laparoscopic and abdominal surgery in patients with stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. CLINICAL TRIALS: The ethical approval number is NFEC-2017-135, and the clinical research registration number is CHiCTR1800017778 (International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/).

Genomic insight into the population history of Central Han Chinese.

BACKGROUND: In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies. AIM: To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese. SUBJECTS AND METHODS: We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE, f statistics, qpWave and qpAdm. RESULTS: We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations. CONCLUSIONS: The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese.