Unveiling the temperature-dependent thermoelectric properties of the undoped and Na-doped monolayer SnSe allotropes: a comparative study.

Motivated by the excellent thermoelectric (TE) performance of bulk SnSe, extensive attention has been drawn to the TE properties of the monolayer SnSe. To uncover the fundamental mechanism of manipulating the TE performance of the SnSe monolayer, we perform a systematic study on the TE properties of five monolayer SnSe allotropes such asα-,ß-,γ-,δ-, andε-SnSe based on the density functional theory and the non-equilibrium Green's functions. By comparing the TE properties of the Na-doped SnSe allotropes with the undoped ones, the influences of the Na doping and the temperature on the TE properties are deeply investigated. It is shown that the figure of meritZTwill increase as the temperature increases, which is the same for almost all the Na-doped and undoped cases. The Na doping can enhance or suppress theZTin different SnSe allotropes at different temperatures, implying the presence of the anomalous suppression of theZT. The Na doping inducedZTsuppression may be caused basically by the sharp decrease of the power factor and the weak decrease of the electronic thermal conductance, rather than by the decrease of the phononic thermal conductance. We hope this work will be able to enrich the understanding of the manipulation of TE properties by means of dimensions, structurization, doping, and temperature.

Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

[Clinical characteristics and literature review of ectopic gastric mucosa in the small intestine].

The study aims to summarize the clinical characteristics of patients with ectopic gastric mucosa in the small intestine, comparing clinical presentation differences between domestic and foreign patients through literature review. The clinical characteristics of cases diagnosed with ectopic gastric mucosa in the small intestine at Peking Union Medical College Hospital from January 2000 to January 2024 were retrospectively analyzed. By searching databanks, such as PubMed, EMBASE, the Cochrane Library, Wanfang, VIP, CNKI, and etc (the inclusion period was from the establishment of the database to January 1, 2024). The literature review was conducted on ectopic gastric mucosa in the small intestine. A total of 10 cases were included, all male, age [M (Q1, Q3)] was 27 (13-69) years old. Gastrointestinal bleeding was the first manifestation in most cases, with severe cases leading to hemorrhagic shock. Abdominal CT indicated local intestinal wall thickening and luminal narrowing in 3 cases. Four cases lesions were located at the beginning of the jejunum and 6 lesions were located in the end segment of ileum. All cases underwent local lesion resection, with postoperative pathology confirming ectopic gastric mucosa. Symptoms disappeared postoperatively, with a follow-up period of 0.5-3.0 years. Literature review indicates that the main clinical manifestation of gastric mucosa ectopia in the small intestine in China is gastrointestinal bleeding, while foreign patients are often complicated with intestinal duplication and intussusception, with abdominal pain and vomiting as the primary and main symptoms. The occurrence rate of intestinal obstruction in female patients, both domestically and abroad, is higher than that in male patients. The occurrence rate of ileal lesions with intestinal obstruction and small intestinal duplication is higher than that of duodenal lesions in both domestic and foreign patients. Local small intestine resection is an effective treatment method with generally good prognosis. Ectopic small intestinal mucosa is relatively rare, with symptoms of gastrointestinal bleeding and intestinal obstruction being common presentations, which can serve as one of the differential diagnoses for unexplained gastrointestinal bleeding.

[Analysis of clinical manifestations and prognosis of primary systemic light chain amyloidosis with liver involvement].

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results: The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 µmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2µmol/L group (0.178 years, 0.195 years) than with the TBil<34.2µmol/L group (0.750 years, 3.586 years) (P < 0.05). Conclusion: Mayo stage and hyperbilirubinemia are inferior prognostic factors for patients with primary systemic light chain amyloidosis accompanied with liver involvement.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

Spin-dependent thermoelectric transport properties of Cr-doped blue phosphorene.

We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.

Electronic structures, transport properties, and optical absorption of bilayer blue phosphorene nanoribbons.

Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.

[Efficacy and safety analysis of a combination regimen with BCL-2 inhibitor in relapsed/refractory primary systemic light chain amyloidosis with t(11;14) from a single center].

Objective: To explore the efficacy and safety of BCL-2 inhibitor-based treatment in patients with relapsed/refractory t (11; 14) primary systemic light chain amyloidosis. Methods: This was a retrospective case series study. Ten patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis who had all received treatment with a combination regimen including the BCL-2 inhibitor venetoclax from January 2018 to November 2022 at the Hematology Department of Peking University People's Hospital were included. Adverse events, and hematological and organ responses were evaluated. Results: The median age of the ten enrolled patients was 59 (range 41-78) years, and the male to female ratio was 8∶2. Except for one patient, a very good partial or better response was achieved in 8/9 patients and one patient obtained a partial response. The overall response rate was 100%. The median time to achieve a hematological response was 60 (range 24-236) days. At least one organ response was observed in 7/9 patients. With a median follow-up of 18 months, one patient experienced hematological progression and one patient died. Grade 3 adverse events included lymphocytopenia (3 cases), anemia (1 case), diarrhea (1 case), and appendicitis (1 case). One patient died of pulmonary fungal infection two months after completion of treatment, which was not excluded as being treatment related. Conclusion: A combination regimen including BCL-2 inhibitors in patients with relapsed/refractory t(11;14) primary systemic light chain amyloidosis is a potentially safe and effective treatment option that warrants further investigation.

[Pediatric myofibroma/myofibromatosis of the soft tissue and bone: a clinicopathological analysis of 28 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myofibroma/myofibromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.

[Radiation-associated sarcomas of bone and soft tissue: a clinicopathological analysis of 46 cases].

Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.

[Mutation characteristics of osteosarcoma: a single center study of 64 cases using next-generation sequencing].

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.

Perinatal and neurodevelopmental outcome in complicated monochorionic pregnancy after selective fetal reduction: radiofrequency ablation vs microwave ablation.

OBJECTIVES: To summarize our experience in the application of radiofrequency ablation (RFA) and microwave ablation (MWA) for selective fetal reduction in complicated monochorionic pregnancies and compare the perinatal outcome of the two techniques. METHODS: This was a retrospective study of data from a consecutive cohort of all monochorionic twin pregnancies that underwent selective fetal reduction with RFA or MWA at Peking University Third Hospital, Beijing, China from January 2012 to December 2018. All surviving cotwins were followed up to assess their neurodevelopment using the Age & Stage Questionnaire, Chinese version. Perinatal and neurodevelopmental outcomes were compared between the RFA and MWA groups. We also fitted multivariable models to test the association between procedure-related factors and the main perinatal outcomes, including preterm birth (PTB) < 37 weeks' gestation, intrauterine fetal death (IUFD) of the cotwin, adverse outcome (defined as occurrence of IUFD of the cotwin, termination of pregnancy or PTB < 28 weeks) and overall survival. RESULTS: In total, 45 cases (42 twin and three triplet pregnancies) underwent RFA and 126 cases (105 twin and 21 triplet pregnancies) underwent MWA. The overall survival rates in monochorionic diamniotic twin pregnancies were similar between the RFA and MWA groups (61.0% vs 67.0%; P = 0.494). However, pregnancies whose indication for fetal reduction was selective intrauterine growth restriction or twin reversed arterial perfusion had higher overall survival rates (75.5% and 82.6%, respectively) compared with those in other indication groups. A total of 104 children were followed up (20 in the RFA group and 84 in the MWA group); four (20.0%) and eight (9.5%) children were assessed as having overall developmental delay in the RFA and MWA groups, respectively, with no significant difference between the two groups. Multivariable analyses showed that procedure indication, number of ablation cycles and gestational age at procedure were associated significantly with the main perinatal outcomes. CONCLUSIONS: RFA and MWA for selective fetal reduction in complicated monochorionic pregnancies can achieve similar overall survival rate and neurodevelopmental outcome, but MWA is associated with a lower risk of preterm birth. Moreover, procedure-related factors are associated significantly with perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

[Retrospective analysis of short-term curative effect of total laparoscopic loop ileostomy reversal after radical resection of rectal cancer].

Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.

[A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia].

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

[Correlation of clinical joint function with histopathological features of knee joint fibrosis].

Objective: To investigate the correlation between the joint function and the histologic grading after total knee arthroplasty, to aid in the early diagnosis and prognostication of arthrofibrosis. Methods: A total of 29 patients including 22 females and 7 males were enrolled retrospectively from October 2015 to October 2020. These patients had a mean age of 63 years (range 41 to 79 years) and underwent total knee revision in Jishuitan Hospital due to joint contraction or loss of range of motion. Histologic assessment was carried out by utilizing immunohistochemistry (IHC) and the Masson staining to evaluate the fibrosis and inflammation of the samples. Results: By light microscopy, early stage arthrofibrosis showed massive proliferation of myofibroblasts and fibroblasts with SMA expression by IHC. In late stage arthrofibrosis, hyaline degeneration occured with extensive hyperplasia of fibrosis-related tissue. The arthrofibrosis samples appeared blue with Masson staining. Lymphocytes showed perivascular distribution. The arthrofibrosis tissue was mostly grade 3 (26 samples) in histologic assessment, moderate grade (25 samples) in ALVAL score, and grade 1 (23 samples) in lymphocyte grading. Fibrosis grading showed an overwhelming correlation with range of motion (ROM) of the joint. The ALVAL score was highly correlated with the WOMAC score. There was also a direct correlation between inflammatory cell infiltration and pain. The fibrosis grading joint with ALVAL score showed a good predictive value of joint function after joint replacement surgery. Conclusions: The histologic assessment score is closely correlated to the joint function with predictive values for the prognosis after joint replacement surgery.

Pharmacogenetic information in Swiss drug labels - a systematic analysis.

Implementation of pharmacogenetics (PGx) and individualization of drug therapy is supposed to obviate adverse drug reactions or therapy failure. Health care professionals (HCPs) use drug labels (DLs) as reliable information about drugs. We analyzed the Swiss DLs to give an overview on the currently available PGx instructions. We screened 4306 DLs applying natural language processing focusing on drug metabolism (pharmacokinetics) and we assigned PGx levels following the classification system of PharmGKB. From 5979 hits, 2564 were classified as PGx-relevant affecting 167 substances. 55% (n = 93) were classified as "actionable PGx". Frequently, PGx information appeared in the pharmacokinetics section and in DLs of the anatomic group "nervous system". Unstandardized wording, appearance of PGx information in different sections and unclear instructions challenge HCPs to identify and interpret PGx information and translate it into practice. HCPs need harmonization and standardization of PGx information in DLs to personalize drug therapies and tailor pharmaceutical care.

Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model.

BACKGROUND: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. RESULTS: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. CONCLUSION: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.

Identification of a large dataset of SNPs in hair-fin anchovy (Setipinna tenuifilis) based on RAD-seq.

Hair-fin anchovy (Setipinna tenuifilis) is an economically important fish distributed in the West Indian Ocean and the Northwest Pacific Ocean. In this study, 154 individuals in eight populations of S. tenuifilis were sequenced and 850 million raw reads were obtained using restriction site-associated DNA sequencing (RAD-seq). First, we identified 14 012 044 hypothetical SNP markers. A dataset of 199 903 high-quality SNPs was collected after further screening. These SNPs have a strong ability to test the genetic diversity between the eight populations. The differentiation and genetic law between samples were explored based on SNPs in populations of S. tenuifilis. The results of this study will provide data for protecting the genetic resources of the species.

[DNA sequencing of H3F3A mutations in H3.3 immunohistochemistry-negative giant cell tumors of bone].

Objective: To investigate the subtypes of H3F3A DNA mutation in H3.3 immunohistochemistry (IHC) negative giant cell tumors of bone (GCTB). Methods: IHC expression of G34W mutated protein was evaluated in 181 cases GCTB. In H3.3 IHC negative cases, Sanger DNA sequencing analysis was used to detect the subtypes H3F3A mutations. Results: Overall, 164 (90.61%) cases of GCTB showed nuclear expression of H3.3, and 17 cases were negative. These 17 H3.3 negative cases were subjected to Sanger DNA sequencing analysis; results showed that eight presented rare mutation subtypes occurring at glycine 34 to leucine (G34L, 3/181, 1.66%), glycine 34 to valine (G34V, 3/181, 1.66%) and glycine 34 to arginine (G34R, 2/181, 1.10%), and the other nine cases were wild type (glycine 34, 9/181, 4.97%). Sanger DNA sequencing analysis confirmed the absence of G34W mutation in the H3.3 negative cases. Combining IHC and DNA sequencing analysis increased the detection rate of H3F3A mutation in the GCTB to 95.03%. Conclusions: H3.3 IHC could detect H3F3A G34W mutation in GCTB, but not for other rare mutation and wild types loci.

SKA2 promotes proliferation and invasion of hepatocellular carcinoma cells via activating the ß-catenin signaling pathway.

Spindle and kinetochore associated complex subunit 2 (SKA2) is a part of the spindle and kinetochore associated (SKA) complex, which has been reported in various cancers, including the breast cancer, lung cancer, and glioma. However, its role remains unclear in hepatocellular carcinoma (HCC). Our study found that SKA2 mRNA levels and immunohistochemistry staining were significantly increased in HCC tissues compared with normal tissues. The role of SKA2 in cell proliferation and invasion was also determined. Overexpression of SKA2 significantly promoted cell proliferation and invasion, while knocking down of SKA2 expression inhibited the growth and invasion of HCC cells. In experiments investigating the underlying mechanism, overexpression of SKA2 may increase the expression levels of total ß-catenin, and knockdown of SKA2 may decrease the expression levels of total ß-catenin. Our studies thus suggest that SKA2 may promote proliferation and invasion of hepatocellular carcinoma cells by activating the ß-catenin signaling pathway, which can serve as a potential target in the diagnosis and/or treatment of HCC.