Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

Lifetime prediction of encapsulated CdSexS1-x quantum platelets for color conversion in high luminance LED microdisplays.

The LED technology is seen today as the most promising approach to manufacture high luminance color microdisplays for augmented reality application. So far, it mostly involves blue micro-LED technology and quantum dots-based layers for green and red color generation by light down-conversion. Despite significant progress, the viability of this technology still raises many questions. Among them, the stability of the color conversion layer under nominal display operating conditions is still an issue which has not been thoroughly addressed yet. This paper provides experimental data on the aging behavior of CdSexS1-x quantum platelets (QP) for blue-to-red conversion, under a wide range of blue irradiation power. A modeling of the photoluminescence (PL) decrease versus aging time is proposed, that enables to reliably predict the lifetime of a color LED microdisplay in real operating conditions. At room temperature, the alumina encapsulated CdSexS1-x QPs exhibit a lifetime (t70) of 35,000 h under operating conditions representative of a microdisplay emitting 100,000 nits white light, in video mode. With an average daily use of 3 hours, it would represent for a microdisplay more than 30 years. In addition, the study highlights that display heating induces a lifetime decrease related to a thermally activated enhancement of the annihilation rate of PL emission centers. As a result, a display operated at 100,000 nits and 45°C would see its lifetime t70 reduced by a factor 4 (∼8 years), which remains acceptable for most micro-display applications.

[Clinical epidemiological survey of primary liver cancer in Yunnan province from 2005 to 2014].

Objective: To investigate the clinical characteristics and changing trends of primary liver cancer in Yunnan province from 2005 to 2014, in order to provide theoretical basis for the prevention and treatment of liver cancer in this region. Methods: A retrospective survey was used to select inpatient cases of liver cancer who were initially diagnosed and treated in our hospital from 2005 to 2014 with simple random sampling. Patients socio-demographic and clinicopathological characteristics were extracted by a unified and standardized questionnaire, and the data were statistically analyzed. Results: A total of 1000 cases with liver cancer were included, aged (53.2±11.2) years, with a male-to-female ratio of 5.99/1.00. There was no significant change in the gender and age composition ratio of patients in the past 10 years. The proportion of patients with lower education level (primary or junior high school) were increased from 21.8% to 23.4%, and the proportion of patients with relatively higher education level were decreased from 58% to 38.2% (P<0.001). Smokers and non-smokers patients were decreased and increased from 58.8% to 44.4%, and 41.2% to 55.6% (P<0.001). The proportion of drinker patients were decreased from 46.4% to 35.2%. The proportion of patients with advanced liver cancer (stage C and D) were increased, while the proportion of patients with stage A and B showed a downward trend (P<0.001). The proportion of HBsAg-positive patients showed an upward trend, that is, rising from 69% in 2005 to 82% in 2014 (P=0.043). The proportion of HBeAg-positive patients showed a steady trend (P=0.008). The use rate of ultrasound examination in patients with liver cancer were decreased from 91.0% to 58.0% (P=0.001), while the use rate of computed tomography (CT), MRI, and PET/CT examinations were increased from 81.0% to 84.0% (P=0.05), 0 to 22% (P<0.001), and 0 to 3% (P=0.026) between 2005 to 2014. The proportion of surgical patients were increased (P=0.005), but the proportion of interventional patients did not change significantly (P=0.590). Surgery and interventional therapy were the most common treatment methods, and the proportion of patients treated with surgery over the past 10 years showed an upward trend (P=0.005), while the proportion of interventional therapy remained at a high level with no significant change (P=0.590). Conclusion: In Yunnan province, the incidence of liver cancer increases with age, and the proportion of male with liver cancer is almost six times that of women. Moreover, the low positive rate of alpha-fetoprotein levels and advanced clinical stage in this region are presently the main challenges against the liver cancer prevention and treatment. The application scope of CT, magnetic resonance imaging, PET-CT and other examination methods has gradually expanded, but the treatment methods are still mainly surgery and interventional therapy.

[Predictive value of combined detection tumor markers in the diagnosis of lung cancer].

To evaluate the predictive value of combined five tumor markers (TMs) CEA, NSE, SCCA, CYFRA21-1 and ProGRP in the diagnosis of lung cancer(LC). Total of 305 hospitalized patients with LC were enrolled, 100 healthy subjects and 100 patients with benign lung diseases were selected as the healthy control (HC) group and BLD group, respectively. The levels of TMs in serum were detected by Flow fluorescence technique. Positivity rates were analyzed by using Chi-square test,The differences of tumor marker levels were compared using Mann-Whitney test and Kruskal-Wallis test. The Receiver Operating Characteristics (ROC) curve was performed to analyze the diagnosis efficacy of TMs. The combined detection had a higher positive rate in patients with LC, adenoadenocarcinoma, squamous cell carcinoma and SCLC (70.82%, 64.74%, 76.4% and 81.03%, respectively) than each TM considered individually. The serological levels of CEA, NSE, SCCA, CYFRA21-1 in LC group were higher than HC and BLD group. The differences of them among the three groups were statistically significant (χ²=90.599, 32.802, 8.473, 40.397 respectively, all P values were<0.05), ProGRP level had no remarkable difference (χ²=3.366, P>0.05), whereas ProGRP level in SCLC were significantly higher compared with adenocarcinoma (Z=6.404,P<0.001) and squamous cell carcinoma (Z=5.765,P<0.001) group. The combined detection difference of positive rate between the early stages(stageⅠ and stage Ⅱ)and the advanced stages (stage Ⅲ and stage Ⅳ) were statistically significant(χ²=24.941, P<0.001).The positive rate of combined detection in the diagnosis of lung cancer lymph node metastasis(76.31%) or distant metastasis(78.18%) was significantly higher than that of single detection. Meanwhile, the positive rate of combined detection in patients with lymph node metastasis or distant metastasis was significantly higher than that in patients without metastasis(χ²=24.60, 9.50 respectively, all P values were<0.05).The combined detection had a better sensitivity(70.82%), accuracy(69.10%)and negative predictive value (59.91%)in LC group than each TM considered individually.The ROC curve showed that the AUC of combined detection in the diagnosis of LC, lung adenocarcinoma, lung squamous cell carcinoma and SCLC were 0.769, 0.780, 0.766 and 0.831, respectively.The combined detection of five tumor markers of CEA, NSE, SCCA, CYFRA21-1 and ProGRP by flow fluorescence technique can improve the diagnostic efficiency of lung cancer.

[Analysis of EGFR mutation and clinical features of lung cancer in Yunnan].

Objective: To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment. Methods: Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital. Results: The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men (P<0.001) and displayed a downward trend with age (P=0.03). The mutation rate of ethnic minorities was higher than Han (P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history (P<0.001), and patients without drinking history was higher than patients with drinking history (P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history (P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types (P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients (P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples (P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area (P<0.001). Multivariate analysis showed that gender (P<0.001), age (P=0.036), smoking history (P<0.001), pathological type (P<0.001), specimen type (P<0.001), and whether or not Xuanwei area (P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area (P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han (P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities (P=0.005). Conclusions: The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

[Driver genes expression and clinical characteristics of targeted therapy in non-small cell lung cancer in Yunnan-Kweichow Plateau].

Objective: To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas. Methods: A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions. Results: The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender (P<0.001), smoking history (P<0.001), age (P<0.001), pathological type (P<0.001), and whether the Xuanwei area (P=0.027), but not related to the nationality (P=0.748) and family history of lung cancer (P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males (P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females (P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority (P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area (P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area (P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area (P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history (P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history (P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history (P=0.008). Conclusions: The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

[Analysis of colorectal cancer screening results in Kunming from 2014 to 2017].

This study analyzed the distribution of high-risk population, the compliance and detected lesions of colorectal cancer screening from the Cancer Screening Program in urban areas of Kunming,Yunnan Province from 2014 to 2017. A total of 127 960 residents were included,of which 14 791 (11.70%) cases were diagnosed with high risk of colorectal cancer by the National Cancer Center High Risk Population Assessment System. A total of 3 484 cases completed colonoscopy clinical screening and the rate of participation was 23.55%. The screening results showed that 592 positive cases were detected, and the positive rate was 17.17%. The detection rates of polyps,adenomas,advanced adenomas,precancerous lesions and colorectal cancer were 16.27%,13.12%,7.18%,7.63% and 0.26%, with 567, 457, 250, 266 and 9 cases, respectively.

Association of betel nut chewing with exercise performance in a military male cohort: the CHIEF study.

INTRODUCTION: Betel nut chewing may cause obesity, neurohormonal activation and inflammation, possibly impairing exercise performances. METHODS: We examined the cross-sectional association in 4388 military male adults aged 18-50 years from the cardiorespiratory fitness in armed forces study in Taiwan between 2013 and 2014. The status of betel nut chewing was classified as current and former/never based on each participant's response to a questionnaire. Physical fitness was evaluated by three basic exercise tests including 3000 m running, 2 min sit-ups and 2 min push-ups. Multiple logistic regression for the best 10% and the worst 10% performers in each exercise, and linear regression were used to determine the relationship. RESULTS: There were 564 current chewers and 3824 non-current chewers for the analysis. The linear regression shows that current betel nut chewing was positively correlated with 3000 m running duration (r=0.37, p=0.042) after adjusting for age, service specialty, body mass index, exercise frequency and alcohol intake. In addition, the logistic regression shows that as compared with non-current chewers, current chewers had lower odds of being the top 10% performers in 2 min push-ups and higher odds of being the bottom 10% performers in 2 min sit-ups (ORs and 95% CIs: 0.71 (0.50 to 0.99) and 1.32 (1.00 to 1.75), respectively). However, the associations between betel nut chewing and physical fitness were all insignificant after further adjusting for current smoking. CONCLUSIONS: Our findings suggest that the impairment of physical fitness associated with betel nut chewing of military young men might be mainly mediated or moderated by the coexisted cigarette smoking.

[Clinical outcomes of cervical disc herniation treated by posterior percutaneous endoscopic cervical discectomy].

Objective: To evaluate the clinical outcomes of posterior percutaneous endoscopic cervical discectomy (PPECD) for cervical disc herniation. Methods: A total of 23 patients who underwent PPECD for cervical disc herniation at Department of Spine Surgery, Guangdong Provincial Hospital of Chinese Medicine from August 2014 to April 2016 were reviewed. The mean age of the 17 males and 6 females was 49.5 years (range from 31 to 61 years). All patients had unilateral upper limb radiating symptoms, 13 patients with right upper limb radiating pain and 10 patients with left upper limb radiation pain, 17 patients with neck pain symptoms. Responsible segment: left C(4-5) 1 case, right C(4-5) 2 cases, left C(5-6) 4 cases, right C(5-6) 8 cases, left C(6-7) 5 cases, right C(6-7) 3 example.Operating time, length of hospitalization, complications, neck and arm Visual analog scale(VAS), and Neck Disability Index(NDI) were evaluated. The excellent and good rate of surgery was evaluated by using the Odom criteria. Harrison method was used to measure cervical curvature. The Cobb angle of the surgical segment was measured on the X-ray, and the range of motion (ROM) was calculated. The changes of the cervical curvature and the surgical segment ROM were compared pre- and post-operation. Results: The operation time was 94.1 min (range from 80 to 150 min). The average length of hospital stay was 4.8 days. The mean follow-up period was 23.5 months (range from 15 to 35 months). The preoperative arm VAS score was 6.95±0.88, 1-week postoperative arm VAS score was 2.09±0.67, the last follow-up arm VAS score was 1.04±0.98. The preoperative neck VAS score was 3.04±0.77, 1-week postoperative neck VAS score was 1.52±0.51 and the last follow-up neck VAS score was 0.61±0.78. The 1-week postoperative and last follow-up arm and neck VAS scores were significantly reduced compared with pre-operation (P<0.01). Compared with 1 week after surgery, the last follow-up of the arm and neck VAS score further reduced, the difference was statistically significant (P<0.01). The preoperative NDI was (58.52±4.98)%, the 1-week postoperative NDI was (33.74±4.72)%, the last follow-up NDI was (19.22±3.23)%. The 1-week postoperative and last follow-up NDI was significantly improved compared with pre-operation (P<0.01). Compared with 1 week after surgery, the last follow-up of the NDI further improved, the difference was statistically significant (P<0.01). The 1-week postoperative cervical curvature was (14.65±2.89)°, and it was improved compared with preoperative(14.23±3.06)°, the difference was statistically significant (P<0.05) . The last follow-up was cervical curvature(14.64±2.68)°, there was no significant difference compared with preoperative (P> 0.05). The preoperative surgical ROM was(5.37±1.83)°, 1-week postoperative was(5.53±1.52)°, and the last follow-up was (5.62±1.48)°, there was no significant difference pre-operative and post-operation (P> 0.05). The excellent and good rate was 91.3% (excellent in 16 cases, good in 5 cases, 2 cases). There was no nerve root injury, cerebrospinal fluid leakage, wound infection, and other complications. Conclusions: PPECD is a sufficient and safe supplement for cervical disc herniation, its recent clinical efficacy was good. And it has no significant effect on cervical stability.

Unveiling attenuation structures in the northern Taiwan volcanic zone.

This cutting-edge study delves into regional magmatism in northern Taiwan through advanced 3-D P- and S-wave frequency-dependent attenuation tomography. Positioned at the dynamic convergence boundary between the Philippine Sea Plate and the Eurasian Plate, Taiwan experiences moderate earthquakes and intriguing volcanic activity, with a focus on the Tatun volcano group. Employing the Formosa seismic array for high-resolution results, our research identifies high-attenuation anomalies (low Q) beneath the northern Taiwan volcanic zone (NTVZ) and offshore submarine volcanoes, indicative of potential hydrothermal activities and magma reservoirs at varying depths. Additionally, we explore low-attenuation anomalies (high Q) in the forearc region of the Ryukyu subduction zone, suggestive of partial saturation linked to serpentinization processes resulting from seawater infiltration or forearc mantle hydration. These findings shed light on the complex geological features and provide essential insights into the crustal properties of northern Taiwan, contributing to a deeper understanding of its magmatic evolution and tectonic processes.

Expression of Toll-like receptors 2 and 4 and the OPG-RANKL-RANK system in inflammatory external root resorption and external cervical resorption.

AIM: To investigate and compare the expression of the pathogen recognition receptors Toll-like receptor (TLR) 2 and TLR4, and the hard tissue resorption triad osteoprotegerin (OPG)-receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) in external inflammatory root resorption of endodontic origin (ER) and external cervical root resorption (ECR) by immunohistochemistry. METHODOLOGY: Formalin-fixed, paraffin-embedded archival specimens collected from teeth that were diagnosed clinically, radiographically and histopathologically with either ER (n = 9) or ECR (n = 9) were processed for immunohistochemistry to investigate and compare levels of TLR2, TLR4, OPG, RANKL, RANK, CD3, CD19 and CD83 expression. The histological features were evaluated via haematoxylin and eosin stain. Taylor's modification of the Brown and Brenn Gram stain was used for examining the presence and distribution of bacteria. All stained slides were digitally photographed and qualitatively analysed, and F test and unpaired Student's t-test were used for statistical analysis. RESULTS: Both ER and ECR showed similar immuno-histopathology characteristics of a fibrovascular connective tissue with varying degrees of inflammatory infiltrate consisting of T and B lymphocytes, dendritic cells, polymorphonuclear lymphocytes and plasma cells. Colonies of bacteria were identified in the majority of lesions, and this correlated with the cellular expression of TLR2 and TLR4 in all lesions. Similarly, all lesions showed a significantly higher (P < 0.05) level of cells expressing RANKL than OPG, indicating hard tissue resorption processes where active in the lesions. CONCLUSION: The immunohistopathology patterns of ECR samples were consistent with the bacteria-driven ER specimens, suggesting bacteria-induced inflammation may be involved in ECR.

Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-ß1 (TGF-ß1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-ß1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-ß1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-ß1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO.

Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus.

Exophiala spinifera can induce both phaeohyphomycosis and chromomycosis. To date there have been 18 human infections caused by E. spinifera in the English literature. A case of E. spinifera-induced phaeohyphomycosis in a patient with systemic lupus erythematosus (SLE) is described. Direct microscopic examination of the pus showed branched, septate and chained hyphae and spores. A dark green velvety colony grew on Sabouraud dextrose agar. Slide culture showed branched, septate hyphae and spine-like annellated conidiophores. Histopathological biopsy revealed yellowish brown hyphae and spores. The isolate was identified as E. spinifera by DNA sequence analysis. The strain was unable to liquefy gelatin, grew at 25°C to 39°C, and was sensitive to itraconazole, amphotericin B, and terbinafine. To our knowledge, this is the first case of cutaneous phaeohyphomycosis caused by E. spinifera in SLE patients.

Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome.

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.

MiRNA-128-3p induces osteogenic differentiation of bone marrow mesenchymal stem cells via activating the Wnt3a signaling.

OBJECTIVE: To clarify the biological function of miRNA-128-3p in influencing the progression of osteoporosis by inducing osteogenic differentiation of MSCs via activating the Wnt3a signaling. PATIENTS AND METHODS: Dynamic expression levels of miRNA-128-3p in osteogenically differentiated MSCs at the different time points were detected by qRT-PCR. The binding sites in the seed sequence of miRNA-128-3p and Wnt3a were predicted using the bioinformatic tool, and their interaction was further confirmed by Dual-Luciferase reporter assay. Co-regulation of miRNA-128-3p and Wnt3a on relative levels of osteogenesis-associated genes, ALP activity and mineralization ability in glucocorticoid-induced MSCs were assessed. RESULTS: MiRNA-128-3p was gradually upregulated with the prolongation of osteogenic differentiation of MSCs. Overexpression of miRNA-128-3p reversed the declines in glucocorticoid-induced expression levels of osteogenesis-associated genes (Bglap, RUNX2 and BMP-2), ALP activity and mineralization ability in MSCs. Wnt3a was able to bind miRNA-128-3p. Its level was positively regulated by miRNA-128-3p in MSCs. Enhanced ALP activity and mineralization ability in glucocorticoid-induced MSCs overexpressing Wnt3a were partially abolished by knockdown of miRNA-128-3p. CONCLUSIONS: By positively regulating Wnt3a, miRNA-128-3p alleviates the progression of osteoporosis through inducing osteogenic differentiation of MSCs.

PTH promotes rabbit tibial fracture healing via the Notch signaling pathway.

OBJECTIVE: To explore the effect of parathyroid hormone (PTH) on the expression of Jagged1 in the rabbit tibial fracture healing, and its function and mechanism in this process via the Notch signaling pathway. MATERIALS AND METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group (n=30) and experimental group (n=30). Then, a rabbit tibial fracture model was established. After surgery, the rabbits in experimental group were given 10 µg/kg PTH (1-34) once a day for 5 days a week, while those in control group were given an equal volume of normal saline. Six rabbits were randomly selected from each group at 1, 2, 3, 4, and 6 weeks after surgery to collect right tibia specimens. Next, X-ray examination, bone mineral density (BMD) test, histological detection, and serum biochemical test were performed. Additionally, the messenger ribonucleic acid (mRNA) expression levels of Notch1 and Jagged1 in the Notch signaling pathway were measured via polymerase chain reaction (PCR) assay. Their protein levels were detected through Western blotting analysis. RESULTS: The healing and BMD in experimental group were better than those in control group since cortical and medullary bridging was observed in the rabbits of experimental group at the 6th week after surgery. Plasma level of alkaline phosphatase (ALP), P content, and the product of Ca and P significantly increased (p<0.05) in experimental group. The pathological morphology of the calluses stained with hematoxylin-eosin (HE) in experimental group was overtly superior to that in control group. The PCR results revealed that both mRNA and protein levels of Notch1 and Jagged1 were lower in control group than those in experimental group (p<0.05). CONCLUSIONS: PTH (1-34) promotes the rabbit tibial fracture healing by regulating Jagged1 ligand molecules in the Notch signaling pathway.

[Screening of colorectal cancer in Kunming urban residents from 2014 to 2017].

Objective: To explore the screening efficiency of colorectal cancer in urban residents of Kunming, China. Methods: Using the method of cluster sampling, from October 2014 to October 2017, residents of the three jurisdictions of Xishan, Guandu and Chenggong Districts of Kunming city were investigated. The inclusion criteria: (1) resident (for more than 3 years) population of Kunming city aged 40-74 years old; (2) voluntarily participating and receiving colonoscopy; (3) signing informed consent. Based on the Harvard Cancer Risk Index, the questionnaire was built on the consensus of more than 20 years of common cancer epidemiology in China. Through the consensus reached by the multidisciplinary expert panel discussion, a comprehensive evaluation system for cancer risk in China was designed. The high-risk group of colorectal cancer was determined by preliminary screening of the questionnaire, and a free colonoscopy was performed for the appointment to the gastrointestinal endoscopy department of the Yunnan Cancer Hospital. All polypoid lesions and ulcers found by colonoscopy must be biopsied to confirm the diagnosis. χ(2) test or Fisher exact probability method was used to compare the detection of colorectal cancer in 4 groups of 40-49 years old, 50-59 years old, 60-69 years old, and ≥70-years old. Detection of colonoscopy, compliance, pathological examination, pathological diagnosis, and morbidity of colorectal cancer were analyzed. Results: A total of 127 960 people from 40 to 74 years old of urban residents in Kunming city participated in the preliminary screening of the questionnaire, including 59 748 (46.7%) males and 68 212 females (53.3%) with mean age of (53.6±8.6) years old. The 40-49 years old group had the largest number of participants (48 044, 37.5%), followed by the groups of 50-59 years old (42 473, 33.2%), 60-69 years old (34 111, 26.7%), and ≥70 years old (3332, 2.6%). Till October 2017, a total of 14 971 people were screened as at high risk of colorectal cancer, with the high-risk detection rate of 11.7%, and the high-risk detection rate of women was significantly higher than that of men [13.4% (9 109/68 212) vs. 9.8% (5 862/59 748), χ(2)=386.947, P<0.001]. The highest high-risk detection rate was in the 50-59 years group in both gender [men: 11.1% (2202/19 831), women: 15.3% (3034/22 642)]. A total of 3449 people among the high-risk population received colonoscopy examination. The compliance rate of colonoscopy was 23.0% (3449/14 971), and the male compliance rate was 19.8% (1162/5862), which was significantly lower than that of females [25.1% (2287/9109), χ(2)=56.175, P<0.001]. The highest compliance was observed in the 50-59 years group [25.4% (1438/5668)], followed by 40-49 years and 60-69 year group [22.1%(1091/4931) and 22.0%(891/4048), respectively], and the compliance of ≥70 years old group was the lowest [9.0% (29/324)]. Colonoscopy examination revealed 606 cases with lesions, the detection rate of lesions was 17.6%, and the male detection rate was significantly higher than that of females [26.9% (313/1162) vs. 12.8% (293/2287), χ(2)=106.140, P<0.001]. The detection rate of lesions increased with age [40-49, 50-59, 60-69, ≥70: 10.9% (119/1091), 17.5% (252/1438), 25.0% (223/891) and 41.4% (12/29), respectively, χ(2)=79.010, P<0.001]. A total of 584 cases underwent endoscopic excision and pathological diagnosis, and 465 cases (13.5%) of precancerous lesions were detected. The prevalence of precancerous lesions in men was higher than that in women [21.3% (247/1162) vs. 9.5% (218/2287), χ(2)=90.801, P<0.001], the precancerous lesion detection rate increased with age [40-49, 50-59, 60-69, ≥70: 8.0% (87/1091), 14.3% (206/1438), 18.1% (161/891) and 37.9% (11/29); χ(2)=58.109, P<0.001]. A total of 4 patients with colorectal cancer were detected, including 3 males and 1 female. The detection rate of male colorectal cancer was 258.2/100 000, and the female was 43.7/100 000, whose difference was not statistically significant (χ(2)=1.488, P=0.223). There was no significant difference in the detection rate of colorectal cancer among 4 age groups [40-49, 50-59, 60-69, ≥70: 91.7/100 000 (1/1091), 69.5/100 000 (1/1438), 224.5/100 000 (2/891) and 0, respectively, P=0.696]. Conclusions: Screening for colorectal cancer is an important measure to control the onset and death of colorectal cancer. Through the questionnaire risk assessment plus colonoscopy, two-step screening method can improve the screening efficiency and greatly reduce the screening cost.

Brachial-ankle vs carotid-femoral pulse wave velocity as a determinant of cardiovascular structure and function.

Carotid-femoral pulse wave velocity (cf-PWV) is a validated marker of arterial stiffening over the central arteries. Brachial-ankle pulse wave velocity (ba-PWV) integrates the mechanical properties from both the central and peripheral arteries and may be more representative than cf-PWV as arterial load for left ventricle (LV). We compared ba-PWV with cf-PWV for the association of cardiovascular structure and function in 320 subjects with various degrees of abnormality in cardiac structure and function. ba-PWV (by oscillometric technique) and cf-PWV (by tonometric technique) were measured simultaneously, and were highly correlated (r=0.79, P<0.001). Both ba-PWV and cf-PWV were significantly correlated with LV mass, but the correlation was better with ba-PWV (r=0.29 vs r=0.22, P=0.0219). While ba-PWV and cf-PWV were similarly significantly correlated with LV end-systolic elastance and mitral E/A ratio, ba-PWV had better correlation with isovolumic relaxation constant (r=0.34 vs r=0.27, P=0.0202) than cf-PWV. In addition, the correlation was also significantly stronger with ba-PWV than with cf-PWV for other indices of arterial stiffness, including carotid incremental modulus (r=0.59 vs 0.50, P=0.0013), effective arterial elastance (r=0.41 vs r=0.33, P=0.0081) and carotid augmentation index (r=0.38 vs r=0.32, P=0.0368). In conclusion, ba-PWV correlates better with LV mass and diastolic function and other indices of arterial function than cf-PWV, probably because ba-PWV encompasses a greater territory of arterial tree than cf-PWV.

A simulation-aided factorial analysis approach for characterizing interactive effects of system factors on composting processes.

A simulation-aided 2-level factorial analysis approach is proposed to characterize the interactive effects of composting factors (i.e. temperature, moisture, oxygen content and initial biomass concentration) on composting processes. To screen the important effect factors when high-order interactions occur, normal probability plot is applied to the result analysis. The results show that the factors have various effects on the composting process in different stages. At the 24th hour, the factors do not show significant effects on the composting process. At the 72nd hour when the composting process reaches active stage, the factors have important effects on the composting process, and their interactive effects are also significant. At the 144th hour, temperature and oxygen content still have effects on the composting process, but not as significant as those at the active stage. These findings could be useful for guiding composting-process operation and management and developing associated control strategies in different composting stages.

Studies of SARS virus vaccines.

1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.