GenomicKB: a knowledge graph for the human genome.

Genomic Knowledgebase (GenomicKB) is a graph database for researchers to explore and investigate human genome, epigenome, transcriptome, and 4D nucleome with simple and efficient queries. The database uses a knowledge graph to consolidate genomic datasets and annotations from over 30 consortia and portals, including 347 million genomic entities, 1.36 billion relations, and 3.9 billion entity and relation properties. GenomicKB is equipped with a web-based query system (https://gkb.dcmb.med.umich.edu/) which allows users to query the knowledge graph with customized graph patterns and specific constraints on entities and relations. Compared with traditional tabular-structured data stored in separate data portals, GenomicKB emphasizes the relations among genomic entities, intuitively connects isolated data matrices, and supports efficient queries for scientific discoveries. GenomicKB transforms complicated analysis among multiple genomic entities and relations into coding-free queries, and facilitates data-driven genomic discoveries in the future.

Role and intervention of PAD4 in NETs in acute respiratory distress syndrome.

BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a common sepsis-associated injury that can increase postoperative mortality but the mechanism is still unclear. MAIN TEXT: The role of neutrophils in the pathophysiology of sepsis was deeply challenged after the discovery of NETosis, a process resulting in neutrophil extracellular traps (NETs) release. NETs can support thrombin generation and the concept of immunothrombosis has emerged as a new innate response to infection. Immunothrombosis leads to thrombosis in microvessels and supports immune cells together with specific thrombus-related molecules. ARDS is a common sepsis-associated organ injury. Immunothrombosis participates in thrombosis in pulmonary capillaries. Intervention regarding immunothrombosis in ARDS is a key scientific problem. PAD4 is the key enzyme regulating the NET skeleton protein histone H3 to citrulline histone to form NETs in immune thrombosis. This review summarizes NETosis and immunohaemostasis, ARDS and therapeutic opportunities targeting PAD4 via PAD4 inhibitors and lncRNAs potentially, providing future therapies. CONCLUSIONS: We identified and summarized the fundamental definition of ARDS and the concept of immune thrombosis and its composition. NETs activation has become particularly relevant in the formation of immune thrombosis. The taskforce highlighted the intervention targets of PAD4, including noncoding RNAs, potentially providing future therapeutic targets to confront the high postoperative mortality of ARDS.

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China.

BACKGROUND: Neoadjuvant and adjuvant immune checkpoint inhibitor treatments for non-small cell lung cancer (NSCLC) patients with resectable disease have presented promising results. This is a phase I study to evaluate the safety and efficacy of neoadjuvant toripalimab in combination with chemotherapy for NSCLC. METHODS: Treatment-naive patients with resectable NSCLC (stage II-IIIB) received two to four cycles of toripalimab (240 mg, intravenously, q3w) combined with platinum-paclitaxel chemotherapy. Surgical operation was performed approximately 4 weeks after the last cycle. The primary end point was safety. The efficacy endpoints included radiographic and pathological response rates, expression of programmed death ligand 1 (PD-L1) and molecular targets. RESULTS: A total of 11 patients were enrolled, consisting of 2 patients (18%) with adenocarcinoma and 9 patients (82%) with squamous cell carcinoma. All patients received two to four cycles of toripalimab plus chemotherapy and underwent radical resection. Regarding safety, 5 of 11 patients (45%) had neoadjuvant treatment-related adverse events, and 1 patient (9%) experienced grade 3 or worse treatment-related adverse events. Radiographic partial response was achieved in 10 patients, with an objective response rate of 91%. Among 11 patients, 6 (55%) achieved pathological complete response, including 1 PD-L1-negative patient. CONCLUSION: Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy was tolerable and induced a pathological complete response in 55% of resectable NSCLC patients.

Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma.

Our study aimed to explore the efficacy and safety of anlotinib-toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P = .05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P = .02). The new regimen increased tumor-infiltration of CD8+ T and CD3+ T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059).

First Observation of New Flat Line Fano Profile via an X-Ray Planar Cavity.

A new Fano profile of a flat line is achieved experimentally by manipulating the relative amplitude of the continuum path, when q takes the pure imaginary number of -i in the x-ray regime. The underlying mechanism is that the interference term in the scattering will cancel the discrete term exactly. This new Fano profile renders only an observable continuum along with an invisible response to the discrete state of atomic resonance. The results suggest not only a different strategy to invisibility studies which provides a possible tool to identify weaker structures hidden by the strong white line, but also a new scenario to enrich the manipulations of two-path interference and nonlinear Fano resonance.

The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China.

BACKGROUND: The Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein. METHODS: Cell samples were collected by cervical scraped for HPV detecting and typing. HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB. RESULTS: α-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site. CONCLUSIONS: HPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.

Searching for Solar Axions Using Data from the Sudbury Neutrino Observatory.

We explore a novel detection possibility for solar axions, which relies only on their couplings to nucleons, via the axion-induced dissociation of deuterons into their constituent neutrons and protons. An opportune target for this process is the now-concluded Sudbury Neutrino Observatory (SNO) experiment, which relied upon large quantities of heavy water to resolve the solar neutrino problem. From the full SNO dataset we exclude in a model-independent fashion isovector axion-nucleon couplings |g_{aN}^{3}|≡1/2|g_{an}-g_{ap}|>2×10^{-5} GeV^{-1} at 95% C.L. for sub-MeV axion masses, covering previously unexplored regions of the axion parameter space. In the absence of a precise cancellation between g_{an} and g_{ap} this result also exceeds comparable constraints from other laboratory experiments, and excludes regions of the parameter space for which astrophysical constraints from SN1987A and neutron star cooling are inapplicable due to axion trapping.

Genetic variability of human papillomavirus type 39 based on E6, E7 and L1 genes in Southwest China.

BACKGROUND: Human papillomavirus type 39 associated with genital intraepithelial neoplasia and invasive cancers, has a high prevalence in Southwest China. HPV E6, E7 are two main papillomavirus oncoproteins, closely relate to the function of HPV immortalization, cell transformation, and carcinogenesis. L1 is the major capsid protein, can reflect the replication status of the virus in cells and the progression of cervical lesions. The purpose of this study is to reveal the prevalence of HPV 39 and the genetic polymorphisms of HPV39 based on E6, E7 and L1 gene in southwest China. METHODS: Cell samples were collected by cervical scraped for HPV detecting and typing, and HPV39 positive samples were selected out. Important E6, E7 and L1 genes of HPV39 were sequenced and analyzed for the study of HPV39 genetic polymorphisms. Phylogenetic trees were constructed by Maximum-likelihood and Kimura 2-parameters methods in Molecular Evolutionary Genetics Analysis version 6.0. The selection pressures of E6, E7 and L1 genes were estimated by Datamonkey web server. The secondary and three-dimensional structure of HPV39 E6, E7 proteins were created by sopma server and SWISS-MODEL software. RESULTS: 344 HPV39 positive samples were selected from 5718 HPV positive cell samples. Among HPV39 E6-E7 sequences, 20 single nucleotide mutations were detected, including 10 non-synonymous and 10 synonymous mutations; 26 single nucleotide mutations were detected in HPV39 L1 sequences, including 7 non-synonymous and 19 synonymous mutations respectively. 11 novel variants of HPV39 E6-E7 (5 in E6 and 6 in E7) and 14 novel variants of HPV39 L1 were identified in this study. A-branch was the most frequent HPV39 lineage in southwest China during our investigation. Selective pressure analysis showed that codon sites 26, 87, 151 in E6 and 75, 180, 222, 272, 284, 346, 356 in L1 were positively selected sites, as well as codon sites 45, 138, 309, 381 were negative selection sites in L1 gene, E7 has neither positive selection sites nor negative selection sites. A certain degree of secondary and three-dimensional structure dislocation was existed due to the non-synonymous mutations. CONCLUSIONS: Amino acid substitution affected the secondary and three-dimensional structure of HPV39, and resulting in the differences of carcinogenic potential and biological functions as well as the immune response due to the antigen epitopes difference, the antigen epitopes with stronger adaptability in Southwest will be screened out based on the above research results for the later vaccine development. And gene polymorphism of HPV39 in Southwest China may improve the effectiveness of clinical test and vaccine design, specifically for women in Southwest China.

High photosensitivity and external quantum efficiency photosensors achieved by a cable like nanoarchitecture.

The poor intrinsic flexibility of semiconducting ceramic materials hinders their applications in wearable electronics. Here, we present a highly efficient photosensor with extreme levels of bending and repeatable resilience based on cable-like structure. The ZnO@TiO2 cable-like photosensor demonstrates an ultra-high external quantum efficiency (2.82 × 106%) and photosensitivity (1.27 × 105) upon UV light illumination at 254 nm, and a stability of 85% at the small curvature radius of 0.5 mm. Moreover, the ZnO@TiO2 photodetector demonstrates extremely stable flexibility over 1000 bending cycles. This specific nanoscale architecture has future potential applications for soft integrated electronics.

The Study of the Low-Lying Valence-Shell Excitations of Hydrogen Sulfide by Fast Electron Impact.

The valence-shell excitations of hydrogen sulfide have been studied by fast electron impact at a collision energy of 1.5 keV and an energy resolution of about 70 meV. By analyzing the variations of intensity and shape of the feature in the range of 5.0-7.5 eV at different scattering angles, the excitation energy of 5.85 ± 0.01 eV and the line width of 0.80 ± 0.01 eV of the 3b21A2 state have been determined. The generalized oscillator strengths of the valence-shell excitations in the energy range of 5.0-9.2 eV of hydrogen sulfide have been determined from the measured spectra. The corresponding optical oscillator strengths have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have also been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The presently obtained oscillator strengths and integral cross sections have significant applications in the studies of planetary atmospheres and interstellar gases.

Risk factors and the potential of nomogram for predicting hospital-acquired pressure injuries.

This 1:5 case-control study aimed to identify the risk factors of hospital-acquired pressure injuries (HAPIs) and to develop a mathematical model of nomogram for the risk prediction of HAPIs. Data for 370 patients with HAPIs and 1971 patients without HAPIs were extracted from the adverse events and the electronic medical systems. They were randomly divided into two sets: training (n = 1951) and validation (n = 390). Significant risk factors were identified by univariate and multivariate analyses in the training set, followed by a nomogram constructed. Age, independent movement, sensory perception and response, moisture, perfusion, use of medical devices, compulsive position, hypoalbuminaemia, an existing pressure injury or scarring from a previous pressure injury, and surgery sufferings were considered significant risk factors and were included to construct a nomogram. In both of the training and validation sets, the areas of 0.90 under the receiver operating characteristic curves showed excellent discrimination of the nomogram; calibration plots demonstrated a good consistency between the observed probability and the nomogram's prediction; decision curve analyses exhibited preferable net benefit along with the threshold probability in the nomogram. The excellent performance of the nomogram makes it a convenient and reliable tool for the risk prediction of HAPIs.

Quality control of imbalanced mass spectra from isotopic labeling experiments.

BACKGROUND: Mass spectra are usually acquired from the Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for isotope labeled proteomics experiments. In such experiments, the mass profiles of labeled (heavy) and unlabeled (light) peptide pairs are represented by isotope clusters (2D or 3D) that provide valuable information about the studied biological samples in different conditions. The core task of quality control in quantitative LC-MS experiment is to filter out low-quality peptides with questionable profiles. The commonly used methods for this problem are the classification approaches. However, the data imbalance problems in previous control methods are often ignored or mishandled. In this study, we introduced a quality control framework based on the extreme gradient boosting machine (XGBoost), and carefully addressed the imbalanced data problem in this framework. RESULTS: In the XGBoost based framework, we suggest the application of the Synthetic minority over-sampling technique (SMOTE) to re-balance data and use the balanced data to train the boosted trees as the classifier. Then the classifier is applied to other data for the peptide quality assessment. Experimental results show that our proposed framework increases the reliability of peptide heavy-light ratio estimation significantly. CONCLUSIONS: Our results indicate that this framework is a powerful method for the peptide quality assessment. For the feature extraction part, the extracted ion chromatogram (XIC) based features contribute to the peptide quality assessment. To solve the imbalanced data problem, SMOTE brings a much better classification performance. Finally, the XGBoost is capable for the peptide quality control. Overall, our proposed framework provides reliable results for the further proteomics studies.

Concordance Study Between IBM Watson for Oncology and Clinical Practice for Patients with Cancer in China.

BACKGROUND: IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with evidence-based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S. PATIENTS AND METHODS: Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO. RESULTS: Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice. CONCLUSION: Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514. IMPLICATIONS FOR PRACTICE: IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China.

Natural Explanation for 21 cm Absorption Signals via Axion-Induced Cooling.

The EDGES Collaboration has reported an anomalously strong 21 cm absorption feature corresponding to the era of first star formation, which may indirectly betray the influence of dark matter during this epoch. We demonstrate that, by virtue of the ability to mediate cooling processes while in the condensed phase, a small amount of axion dark matter can explain these observations within the context of standard models of axions and axionlike particles. The EDGES best-fit result favors an axionlike particle mass in the (10, 450) meV range, which can be compressed for the QCD axion to (100, 450) meV in the absence of fine tuning. Future experiments and large scale surveys, particularly the International Axion Observatory (IAXO) and EUCLID, should have the capability to directly test this scenario.

Indium-doped SnO2 nanobelts for high-performance transparent and flexible photosensors by a facile assembly.

Flexible and transparent electronics is the emerging future technology for optoelectronic devices. Recently, it has attracted considerable attention from the research community due to its prodigious commercial applications. Herein, we report highly flexible and transparent ultraviolet photosensors based on indium-doped tin oxide nanobelts with enhanced simultaneous photosensitivity and recovery speed, compared to pure SnO2 nanobelts. Optoelectronic properties of the nanobelt photosensors have been found to be strongly related to the indium doping concentration and grain size of the nanobelts. A facile assembly method has been used to prepare the well-aligned nanobelt device for UV photosensors. Excellent flexible properties of the nanobelts have been explored, which show a superior response during bending tests and almost maintain their properties after 300 bending cycles. The enhanced photosensitivity of about 70 times that of undoped SnO2 nanobelts along with a highly enhanced recovery speed of less than 1.75 s have been achieved by the precise doping of In3+ into SnO2 lattice nanobelts. All these results show that our prepared photosensors demonstrate superior mechanical, electrical, and optical properties for their use in flexible and transparent electronics.

Serial stimulated thyroglobulin measurements are more specific for detecting distant metastatic differentiated thyroid cancer before radioiodine therapy.

OBJECTIVE: Preablative stimulated thyroglobulin (ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma (DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin (TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically. METHODS: A total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1 (n=72) and M0 (n=245) according to the presence of distant metastasis (DM) or not. The initial ps-Tg measurement, with a corresponding TSH exceeding 30 µIU/mL, was marked as Tg1, and ps-Tg measured right before radioactive iodine (RAI) therapy was defined as Tg2, with a median interval of 8 days. ΔTg denotes Tg2-Tg1, and ΔTSH denotes TSH2-TSH1. Tg1, Tg2, ΔTg, and ΔTg/ΔTSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic (ROC) curve analysis, and further compared with chest computed tomography (CT) and posttreatment whole-body RAI scan (RxWBS). RESULTS: Compared with single ps-Tg measurement (Tg1 or Tg2), both ΔTg and ΔTg/ΔTSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. ΔTg/ΔTSH manifested a higher accuracy (88.64%) and specificity (90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT (90.20% vs. 66.00%) and a much higher sensitivity than RxWBS (83.33% vs. 61.11%). CONCLUSIONS: Serial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. ΔTg/ΔTSH is a specific early biochemical marker for DM-DTC.

Missed Initial Diagnosis of Malignant Struma Ovarii Containing Follicular Thyroid Carcinoma: Metastatic Pulmonary Recurrence 17 yr After Ovariectomy.

Distant metastasis of rare malignant struma ovarii (MSO) has been reported for cases associated with papillary thyroid cancer but few with follicular thyroid cancer. A 38-yr-old woman with struma ovarii that was initially diagnosed as "benign" presented with pulmonary metastasis and coughing 17 yr later. The lungs lesions were confirmed to be follicular thyroid cancer by biopsy. Rereview of the initial surgical ovary specimens confirmed the condition to be MSO with follicular thyroid cancer. The patient was treated with total thyroidectomy, which showed no thyroid malignancy, followed by (131)I (iodine-131) treatments. Dramatic reduction was observed in both the stimulated thyroglobulin level and the size of the pulmonary metastases over 1 yr. During the following 3-yr follow-up, the patient remained clinically well, with undetectable thyroglobulin (<1 ng/mL) and small stable pulmonary lesions. This is an exceedingly rare case of MSO with follicular thyroid cancer metastasized to the lungs presenting with a late onset but a fortunate excellent response to multidiscipline treatments. It is advisable that struma ovarii be carefully examined to avoid missing malignancy and patients be clinically followed up even with a benign initial diagnosis.

Relationship between Variation of Pre-ablation Stimulated Thyroglobulin and Distant Metastasis in Patients with Differentiated Thyroid Cancer.

OBJECTIVE: To investigate the relationship between the dynamic variation of pre-ablation stimulated thyroglobulin(sTg)and distant metastasis in patietns with differentiated thyroid cancer(DTC). METHODS: DTC patients after total or near total thyroidectomy were divided into two groups as M1 group(n=38)and M0 group(n=130)according to the presence of distant metastases or not. Clinical data including pre-ablation sTg and the corresponding thyrotropin(TSH)values were dynamically measured. The pre-ablation sTg and corresponding TSH collected at the first time were defined as Tg1 and TSH1,while as Tg2 and TSH2 at the last time. χ(2) test was used to compare the variation tendency of sTg between these two groups. Tg1,Tg2,pre-ablation sTg variation(∆Tg),and ∆Tg/∆TSH ratio between M0 and M1 were compared by Mann-Whitney rank-sum test. The receiver operating characteristic(ROC)curves and diagnostic critical point(DCP)were employed to evaluate the predictive values of the above indicators. RESULTS: Both Tg1 and Tg2 of M1 were significantly higher than those of M0(the Mann-Whitney rank-sum test:Tg1 P<0.001,Tg2 P<0.001). The corresponding areas under the ROC curve(AUC)to differentiate the two groups were 0.921 and 0.942,respectively. The cut-off value of Tg2,which was more accurate in predicting distant metastasis,was 24.3 ng/ml with a sensitivity of 92.11% and a specificity of 83.85%. Both ∆Tg and ∆Tg/∆TSH between these two groups were significantly different(the Mann-Whitney rank-sum test:∆Tg P=0.002,∆Tg/∆TSH P<0.001). ∆Tg/∆TSH worked better than Tg2 in predicting distant metastasis with both higher accuracy(87.50%)and higher specificity(86.92%). CONCLUSIONS: Dynamically tracing pre-ablation sTg may improve the accuracy and specificity of distant metastases prediction in DTC patients. ∆Tg/∆TSH,which means the ratio of sTg variation to TSH variation,may be a useful diagnostic marker for predicting distant metastases in DTC.

[Association of single nucleotide polymorphisms in H2BFWT with male infertility in southwest China].

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in exons of H2BFWT gene with male infertility in southwest China. METHODS: Three hundred and twelve infertile men and 211 fertile men were recruited. PCR was employed to amplify the target fragments of H2BFWT, and PCR products were sequenced. Prevalence of SNPs in the two groups was analyzed by statistical method. RESULTS: The detected SNPs have mainly distributed in the first exon of the H2BFWT gene. The ratios of 368G/A (rs553509) and -9C/T (rs7885967) were significantly higher in infertile group than fertile group. Additionally, a context-dependent effect was observed between 368G/A and -9C/T which the allele 368G combined with allele -9T will considerably increase the risk of male infertility. CONCLUSION: The present study has revealed that the SNPs in H2BFWT are associated with male infertility, and may increase the susceptibility of male infertility in southwest China.

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab.

Background: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented. Methods: This case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas. Results: All six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab. Conclusion: Hepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.