[The application of human genetic technology in the medical field urgently needs standardization].

Human gene editing technology is a hot spot and focus in the development of biotechnology, but it has also caused controversies over technical risks, genetic biosecurity, ethical dignity of human society and the legality of application, causing people to worry about the application of this technology. Gene editing for reproductive purposes is generally prohibited internationally, and countries have established legal regulatory systems to regulate the application of gene editing technology according to their own conditions. China shall establish a security risk access system for gene editing technology, ensure national biosecurity, establish and improve the system of ethical norms for scientific research, improve the construction of legislative standardization, and provide legal guarantees for the research and application of gene editing technology.

Performance and reading time of lung nodule identification on multidetector CT with or without an artificial intelligence-powered computer-aided detection system.

AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.

Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors.

BACKGROUND: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors. METHODS: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction. RESULTS: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers. CONCLUSIONS: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

[Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma].

OBJECTIVE: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC). METHODS: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed. RESULTS: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic. CONCLUSION: Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

[Characteristics of lymph node metastasis and evaluating the efficacy of endoscopic submucosal dissection in early gastric cancer].

OBJECTIVE: To investigate the correlation between clinicopathological features and lymph node metastasis, and to evaluate the feasibility and efficacy of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) by comparing with surgery treatment. METHODS: The clinicopathological data of 320 patients with EGC who were treated in Peking University First Hospital between January 2010 and December 2017 were retrospectively reviewed, in which there were 198 cases of surgical procedure and 122 cases of ESD. Characteristics of lymph node metastasis in EGC were analyzed, and lymph node metastasis of EGC with ESD absolute and expanded indications were summarized. The long-term efficacy of ESD and surgical treatment of EGC were compared to evaluate the rationality of absolute and expanded indications of ESD. RESULTS: Lymph node metastasis was detected in 22 (11.1%) of 198 patients. Univariate analysis showed a positive relationship between tumor size (χ2=5.525, P=0.019), depth of invasion(χ2=8.235, P=0.004), histological type (χ2=6.323, P=0.012), lymphovascular invasion (χ2=12.273, P < 0.001) and lymph node metastasis in EGC. Multivariate analysis revealed that depth of invasion(Wald=7.575, P=0.006) and histological type (Wald=6.317, P=0.012) were independent relative factors of lymph node metastasis in EGC. The lymph node metastasis rates of the patients with absolute and expanded ESD indications were both 0%. The 5-year survival rates of the patients who met ESD absolute indication receiving surgery treatment and ESD were 97.6% and 97.9% respectively, and the difference between the two groups was not statistically significant(χ2=0.014, P=0.907).The 5-year survival rates of the patients who met ESD expanded indication receiving surgery treatment and ESD were 96.5% and 91.7% respectively, the difference between the two groups was not statistically significant(χ2=1.061, P=0.303). CONCLUSION: Lymph node metastasis in EGC is mainly correlated with depth of invasion and histological type. Our data indicate that ESD procedure for EGC is comparable to surgery in terms of long-term efficacy in both absolute and expanded indications. However, some studies of a large sample size are still needed for more confirmation.

The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A preliminary assessment.

BACKGROUND AND OBJECTIVE: The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy. MATERIAL AND METHODS: This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1ß), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed. RESULTS: Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1ß and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1ß, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P = .02) for discriminating between the high- and low-responder subgroups. CONCLUSION: Salivary IL-1ß and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment.

Patterns of recurrence after oesophagectomy and postoperative chemoradiotherapy versus surgery alone for oesophageal squamous cell carcinoma.

BACKGROUND: Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies. METHODS: Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival. RESULTS: A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3-4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001). CONCLUSION: Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.

[Predictive value of single nucleotide polymorphisms of HLA-C and UBE2L3 in evaluating the effect of telbivudine antiviral therapy during pregnancy].

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.

[Gα11 expression and effect of sildenafil in muscularization of non-muscular pulmonary arterioles in rat with pulmonary arterial hypertension].

OBJECTIVE: To investigate expression changes and role of Gα11 protein in the processes of muscularization of non-muscular pulmonary arterioles and effect of sildenafil intervention in rats with pulmonary arterial hypertension (PAH). METHODS: Thirty SD rats were randomly divided into three groups, including normal control group, monocrotaline (MCT) group and sildenafil group; PAH model was prepared with 50 mg/kg MCT treatment for 4 weeks in the MCT group, and these rats were treated by 25 mg/kg sildenafil for 2 weeks after PAH formation in the sildenafil group, and the normal control group were treated with the equal amounts of physiological saline instead of monocrotaline; pulmonary artery pressure was measured with jugular vein catheterization; hematoxylin and eosin (HE) staining method was used to detect the pulmonary arteriolar morphology and vascular tissue parameters; expression of the target Gα11 protein, vascular smooth muscle marker osteopontin (OPN) and proliferation marker proliferating cell nuclear antigen (PCNA) was detected by Western blot. RESULTS: Pulmonary artery mean pressure (mPAP), non-muscular pulmonary arterioles wall thickness index (TI) and area index (AI) of the MCT group were higher than those of the normal control group[(27.43±3.97) vs (11.93±1.52) mmHg (1 mmHg=0.133 kPa), 0.49±0.07 vs 0.31±0.09 and 0.74±0.05 vs 0.45±0.10](all P<0.05), and meanwhile the expression levels of Gα11 and the related proteins including OPN and PCNA were significantly enhanced. mPAP, TI and AI[(18.59±1.44) mmHg, 0.39±0.09 and 0.56±0.04]of the sildenafil group were all lower than those of the MCT group (all P<0.05), and furthermore, expressions of Gα11, OPN and PCNA also reduced in line with these changes. CONCLUSION: Gα11 protein plays a role in the development of PAH and pulmonary non-muscular arteriole muscularization, and sildenafil effectively suppresses PAH and pulmonary vascular remodeling by inhibiting Gα11 expression.

Randomised controlled trial on the effectiveness of home-based walking exercise on anxiety, depression and cancer-related symptoms in patients with lung cancer.

BACKGROUND: Although exercise has been addressed as an adjuvant treatment for anxiety, depression and cancer-related symptoms, limited studies have evaluated the effectiveness of exercise in patients with lung cancer. METHODS: We recruited 116 patients from a medical centre in northern Taiwan, and randomly assigned them to either a walking-exercise group (n=58) or a usual-care group (n=58). We conducted a 12-week exercise programme that comprised home-based, moderate-intensity walking for 40 min per day, 3 days per week, and weekly exercise counselling. The outcome measures included the Hospital Anxiety and Depression Scale and the Taiwanese version of the MD Anderson Symptom Inventory. RESULTS: We analysed the effects of the exercise programme on anxiety, depression and cancer-related symptoms by using a generalised estimating equation method. The exercise group patients exhibited significant improvements in their anxiety levels over time (P=0.009 and 0.006 in the third and sixth months, respectively) and depression (P=0.00006 and 0.004 in the third and sixth months, respectively) than did the usual-care group patients. CONCLUSIONS: The home-based walking exercise programme is a feasible and effective intervention method for managing anxiety and depression in lung cancer survivors and can be considered as an essential component of lung cancer rehabilitation.

Diversity and antimicrobial activity of endophytic fungi isolated from Cephalotaxus hainanensis Li, a well-known medicinal plant in China.

UNLABELLED: About 1051 endophytic fungi were isolated from leaves, branches, barks and stems of Cephalotaxus hainanensis Li from four sites in Hainan, China. The fungi were identified as 21 genera by morphology and ITS sequences. One dominant species was Phomopsis quercella in Hainan Tropical Botanical Garden and Bawangling Nature Reserve, with relative frequency of 42·06 and 34·88% respectively. Another dominant species was Colletotrichum boninense in Wuzhishan and Jianfengling Nature Reserves, with relative frequency of 36·84 and 46·97% respectively. Among the selected 21 endophytic fungi, 17 strains (80·95%) had activity against at least one pathogenic bacteria, and 14 strains (66·67%) exhibited activity against at least one fungal pathogens. Neonectria macroconidialis showed strong inhibition against Staphylococcus aureus (inhibition zone being 20 mm), Bacillus subtilis (14 mm) and Streptococcus agalactiae (28 mm). Xylaria sp. showed strong inhibition against Escherichia coli (20 mm), Rhizoctonia solani (20 mm) and Sclerotinia sclerotiorum (17 mm). Verticillium bulbillosum showed great activity against Strep. agalactiae (32 mm) and Fusarium oxysporum (22 mm). These endophytic fungi showed potentials in medicine development. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi from medicinal plants are an important source of novel and viable drugs. Cephalotaxus hainanensis Li is well known for leukaemia treatment and its endophytic fungi were isolated to investigate the diversity and antimicrobial activity. It was found that Ce. hainanensis Li had rich endophytic fungi, and some fungi showed strong antimicrobial activity against certain pathogens. These fungi can be used in medicine development.

Hypoxia inducible factor 2α/insulin-like growth factor receptor signal loop supports the proliferation and Oct-4 maintenance of mouse germline stem cells.

Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α(-/-)) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP(+)GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP(+)GSCs. The hypoxic-AP(+)GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP(+)GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP(+)GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP(+)GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development.

A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis.

OBJECTIVES: To compare the risk of acute coronary syndrome (ACS) between patients with and without ankylosing spondylitis (AS). METHOD: This retrospective cohort study identified all patients with AS aged ≥ 18 years newly diagnosed from 2000 to 2009, registered in the National Health Insurance Research Database (NHIRD) in Taiwan. The non-AS cohort consisted of fourfold randomly selected control patients free of AS, frequency matched by age, sex, and diagnosis year. The incidence of ACS was determined for both AS and non-AS cohorts. RESULTS: We selected 6262 patients with AS and 25 048 patients without AS. The patients with AS were more prevalent than those without, with co-morbidities of hypertension, diabetes mellitus (DM), hyperlipidaemia, stroke, and peripheral vascular diseases. The overall incidence rate of ACS was higher in the AS cohort than in the non-AS cohort (4.4 vs. 2.9 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.36 [95% confidence interval (CI) 1.16-1.59]. AS patients with co-morbidities of hypertension, DM, and cancer had an aHR of 7.74 for ACS, compared to those without these co-morbidities. CONCLUSIONS: AS patients are at higher risk of ACS compared with non-AS subjects. Management of CV risk factors should be taken into account for the treatment of patients with AS, especially for patients with co-morbidities of hypertension, DM, and cancer.

Spontaneous Early Recanalization after Acute Innominate Artery Thromboembolic Occlusion Secondary to Abrupt Aspirin and Statin Discontinuation: A Case Report.

Statin and antiplatelet drugs are widely used for prevention of ischaemic stroke and other cardiovascular diseases in high-risk patients. We report a rare case of a 49-year old man with a history of myocardial infarction and hyperlipidaemia who suffered an acute occlusion of his innominate artery (IA) accompanied by subclavian steal syndrome and cerebral infarction, on day seven after abrupt cessation of aspirin and statin, as confirmed by magnetic resonance and computed tomographic angiography of head and neck, and colour-coded Duplex ultrasonography (CCDU). Aspirin and atorvastatin were immediately re-started on admission. Spontaneous recanalization of IA was shown on repeat CCDU and digital subtraction angiography on day 10 after stroke onset. This case serves as a reminder that abrupt discontinuation of both aspirin and statin in patients with previous history of cardiovascular disease may increase the risk of ischaemic stroke.

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells.

The regeneration of periodontal, periapical, and pulpal tissues is a complex process requiring the direct involvement of cells derived from pluripotent stem cells in the periodontal ligament and dental pulp. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are spatially distinct with the potential to differentiate into similar functional and phenotypic cells. We aimed to identify the cell heterogeneity of DPSCs and PDLSCs and explore the differentiation potentials of their specialized organ-specific functions using single-cell transcriptomic analysis. Our results revealed 7 distinct clusters, with cluster 3 showing the highest potential for differentiation. Clusters 0 to 2 displayed features similar to fibroblasts. The trajectory route of the cell state transition from cluster 3 to clusters 0, 1, and 2 indicated the distinct nature of cell differentiation. PDLSCs had a higher proportion of cells (78.6%) at the G1 phase, while DPSCs had a higher proportion of cells at the S and G2/M phases (36.1%), mirroring the lower cell proliferation capacity of PDLSCs than DPSCs. Our study suggested the heterogeneity of stemness across PDLSCs and DPSCs, the similarities of these 2 stem cell compartments to be potentially integrated for regenerative strategies, and the distinct features between them potentially particularized for organ-specific functions of the dental pulp and periodontal ligament for a targeted regenerative dental tissue repair and other regeneration therapies.

Mechanism studies for relativistic attosecond electron bunches from laser-illuminated nanotargets.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.

Dental diagnostic X-ray exposure and risk of benign and malignant brain tumors.

BACKGROUND: This study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case-control study. MATERIALS AND METHODS: We identified 4123 BBT cases and 16 492 controls without BBT (study 1) and 197 MBT cases and 788 controls without MBT (study 2) from Taiwan National Health Insurance claim data. The risks of both types of tumor were estimated in association with the frequency of received dental diagnostic X-ray. RESULTS: The mean ages were ~44.2 years in study 1 and 40.6 years in study 2. Multivariable unconditional logistic regression analysis showed that the risk of BBT increases as the frequency of received dental diagnostic X-ray increases. The BBT odds ratio increased from 1.33 [95% confidence interval (CI) 1.22-1.44] for those with annual mean X-ray examination of less than one to 1.65 (95% CI 1.37-1.98) for those with three or more X-ray examinations, after controlling for comorbidities. No significant association was found between MBTs and dental diagnostic X-ray exposure. CONCLUSIONS: Exposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.