[Analysis on the imported Coronavirus Disease 2019 related cluster epidemic in rural areas of Chengdu].

An epidemiological investigation was carried out on a local cluster of outbreak caused by imported cases of Coronavirus Disease 2019 (COVID-19) in rural areas of Chengdu in December 2020, to find out the source of infection and the chain of transmission. According to Prevention and Control Protocol for COVID-19 (Version 7), field epidemiological investigation was adopted, combined with big data technology, video image investigation, gene sequencing and other methods to carry out investigation into COVID-19 cases and infections source tracing, analyze the epidemiological association, and map the chain of transmission. From December 7 to 17, 2020, 13 local COVID-19 confirmed cases and 1 asymptomatic case were diagnosed in Chengdu, of which 12 cases (85.71%) had a history of residence and activity in the village courtyard of Taiping (TP), Pidu (P) District, Chengdu. From November 8, 2020 to November 28, 2020, a group of inbound people form Nepal were transferred to the designated entry personnel quarantine hotel of P District which was adjacent to the TP village. During quarantine, there were 5 cases who tested positive for COVID-19. Through gene sequencing alignment, genes of local cases and Nepalese imported cases from the same period are homologous, all belong to the lineage of L2.2.3 (B.1.36 according to Pangolin lineage typing method). According to the results of field epidemiological investigation and gene sequencing analysis, the index case was most likely infected by contact with household waste of quarantine site. Under the situation of normalization prevention and control of COVID-19, sentinel monitoring of fever clinics in primary medical institutions is the key to early detection of the epidemic. The multi-department joint epidemiological investigation and the application of gene technology are the core links of the investigation and traceability of modern infectious diseases. The allocation of public health resources in rural areas needs to be strengthened. We need to improve the capacity for early surveillance and early warning of the epidemic in rural areas.

Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma.

PURPOSE: Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers' features and discussed potential therapeutic implications. METHODS: A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS: Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies. CONCLUSION: Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling.

[Prevalence status and influencing factors of visual impairment in the elderly people in rural areas of Yugan County, Jiangxi Province].

Objective: To assess the prevalence of visual impairment and the influencing factors among rural residents aged 60 years and above in Yugan county, Jiangxi province. Researchers analyzed influencing factors and provided scientific rationale for blindness prevention and control. Methods: Stratified cluster random sampling was used in randomly selecting 3 789 rural residents aged ≥ 60 in Yugan county. Eligible residents were invited to receive ophthalmic examinations and epidemiological investigations. Multivariate logistic regression was performed to analyze any influencing factors. Results: Three thousand seven hundred and eighty-nine rural residents completed the ophthalmic examination and investigation. Based on presenting visual acuity, the prevalence of visual impairment was 24.1%(915), of which blindness and moderate and severe was 2.9%(108) and 21.3%(807). The top five causes ranked are (1) cataract (283, 30.9%), (2) Refractive error (81, 8.9%), (3) macular degeneration (29, 3.2%), (4) Corneal opacity (14, 1.5%). Multivariate logistic regression showed that age, gender, education, occupation, marital status, ophthalmic anamnesis, smoking situation, and daily fruit intake were the main factors that were the influencing factors of visual impairment. Conclusions: The prevalence of visual impairment in the elderly population in rural areas of Yugan County is quite high. Keep a healthy diet, timely correction of eye disease, could reduce the risk of visual impairment. (Chin J Ophthalmol, 2018, 54:605-610).

[A clinical analysis of micafungin treatment of pulmonary invasive fungal infection in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation].

Objective: To investigate the efficacy and safety of micafungin (MCF) for pulmonary invasive fungal disease (PIFD) in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation. Method: Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 (average 6.2±2.0) years. There were 12 cases of acute leukemia (AL) after chemotherapy, 4 cases of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 9 cases of ß-thalassemia major after allo-HSCT. All children received MCM for the treatment of PIFD, the dosage of MCM was 3-4 mg/ (kg·d) , once a day. The children received 2 to 6 courses of treatment, individually with a course of 7 days. 1, 3-ß-D glucan assay (G test), galactomannan antigen test (GM test), high-resolution CT and the biochemical indexes for organ functions were closely monitored. Result: Twenty-five cases were diagnosed as PIFD, including 2 patients diagnosed as proven, 6 as probable and 17 as possible. Of the 25 cases, 1 was confirmed aspergillus by biopsy pathology and 1 was candida albicans by blood culture. The G and GM test with positive results was 5 and 2 respectively. Chest CT scans of the 25 cases had obvious lesions: air crescent sign and cavitation in 4 cases, diffuse ground glass change in 9 cases, double lung scattered patchy, small nodules and cord like high density shadow in 7 cases, unilateral or bilateral chest wall wedge-shaped consolidation edge in 5 cases and pleural effusion in 5 patients. The effective rate of MCF in treatment of PIFD was 68% (17/25), including 13 cases cured, 4 cases improved, 4 cases were improved clinically and in 4 cases the treatment was ineffective. Eight cases were effective in MCF monotherapy group (12 cases) and nine were effective in MCF combined therapy group(13 cases), respectively. Side-effects including allergies, gastrointestinal side effects, electrolyte disturbances, impairment of liver and kidney function, and myelosuppression were not found in those children treated with MCF. Conclusion: Micafungin is effective and safe in the treatment of pulmonary invasive fungal disease in pediatric patients with acute leukemia or post hematopoietic stem cell transplantation.

[Application of bedside ultrasound in measuring gastric residual volume in neurosurgical critical patients with enteral nutrition support].

Objective: To explore the effect of bedside ultrasound in measuring gastric residual volume in neurosurgical critical patients with enteral nutrition support. Method: From March to August 2016, 70 critically neurological patients with continues enteral nutrition who admitted in Intensive Care Unit (ICU) were randomized into two groups. The observation group applied the bedside ultrasound monitoring gastric residual volume every day to guide the implementation of enteral nutrition. The control group used syringes withdrawing every 8 hours to measure the gastric residual volume. Results: There was no statistically significant difference in the incidence of complications include regurgitation and aspiration in this two group patients (P=0.356; P=1.000), while the times of interrupting enteral nutrition was lower in the observation group(25.7% vs 5.7%, 74.3% vs 94.3%, P=0.045), the length of target feeding time and the length of ICU stay, the operation time was shortened, with a statistically significant difference[(2.37±0.69) d vs (3.49±0.74) d, P=0.028; (8.52±5.45) d vs (6.40±2.71) d, P=0.022; (58.29±11.22)s vs (67.60±7.05) s, P=0.000]. Conclusion: The application of bedside ultrasound to measure gastric residual volume can be a scientific method to guide enteral nutrition in neurosurgical critical patients, which can reduce the times of interrupting enteral nutrition and shorten the length of target feeding time and ICU length of stay, reduce the workload of nurses.

Association of EGFR and KRAS mutations with expression of p-AKT, DR5 and DcR1 in non-small cell lung cancer.

The activation of AKT is one of the causes of resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combines with related receptors to trigger apoptosis or protect the cells against TRAIL apoptosis. This research focused on the association of EGFR and KRAS mutations with expression of AKT, p-AKT, DR5 and DcR1 in non-small cell lung cancer. 82 NSCLC patients were included in the study. xTAG liquichip techonolgy (xTAG-LCT) was applied to investigate the genetic mutation of EGFR and KRAS, Quantitative Real-time PCR was used to test the mRNA expression of AKT, DR5 and DcR1 and Western Blot was applied to test the protein expression of AKT, p-AKT, DR5, and DcR1. We found that of 82 patients, 31 cases had EGFR-activating mutations, more common in female, adenocarcinoma, and non-smoker patients; 9 cases had KRAS mutations, frequently found in patients with smoking history. The expression of AKT and p-AKT correlated with staging, tumor differentiation, and lymph node metastasis. The expression of DR5 in phase III and low differentiation tumor was significantly higher than that in phase I+II and high and median differentiation tumor; the expression of DcR1 in phase III and low differentiation tumor was significantly lower than that in phase I+II and high and median differentiation tumor. Compared with EGFR and KRAS wild type, in NSCLC tissue with EGFR and KRAS mutations, the expression of AKT and p-AKT was significantly higher. These results suggest that EGFR and KRAS mutation status was associated with the expression of AKT and p-AKT. AKT, p-AKT, DR5, and DcR1 all took part in the occurrence and development of NSCLC, and may become a reference index to evaluate the prognosis of NSCLC.

[All-trans retinoic acid improves iodine uptake of thyroid cancer cells via repressing transcriptional activity of ß-catenin].

OBJECTIVE: To determine whether all-trans retinoic acid (ATRA) could improve iodine uptake via repressing transcriptional activity of ß-catenin in thyroid cancer cells. METHODS: Three kinds of treatment models were firstly established with alcohol, ATRA, and transfection of ß-catenin shRNA in undifferentiated human thyroid cancer cell line-SW1736.Then the expressions of sodium iodide symporter (NIS), ß-catenin and its regulating factors, epithelial-mensechymal transition (EMT)-phenotype, invasion and metastasis associated proteins were further measured in above three cell models.After that, the influence of ATRA on the functional expression of NIS, iodine uptake potency, tumor growth curve and treatment effect inducing by radioactive iodine was comparatively analyzed in vitro and in vivo trials. RESULTS: After treated with ATRA, transcriptional activity of ß-catenin decreased by downregulating phosphorylation of ß-catenin Ser45, Y654 and GSK-3ß Ser9. Additionally, ATRA effectively upregulated the protein level of NIS, and reversed EMT phenotype in alcohol treated cells, with absence in epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of Vimentin, urinary plasminogen activator (uPA), uPAR and Fibronectin.Compared with alcohol-treated group, both in vitro proliferation and invasion potential of ATRA treated cells markedly decreased (all P<0.05), and iodine uptake in vitro increased about 3.5-folds (P=0.007). In ATRA-treated animal model, tumor growth potential and tumor mass were significantly inhibited by radio-iodine ((131)I) treatment (all P<0.05). CONCLUSIONS: ATRA can increase functional expression of NIS via downregulating transcriptional activity of ß-catenin and promote isotope sensitivity to radio-iodine in human undifferentiated thyroid cancer.

Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells.

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.

Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro.

BACKGROUND: The prognosis of patients with metastasized thyroid carcinoma is not optimistic, necessitating the search for new treatment options. AIM: Beneficial effects of retinoic acid (RA) have been suggested in thyroid cancer differentiation and the present study was performed to investigate the anti-metastatic potential of RA in respect of important determinants of metastatic behavior in thyroid carcinoma, focusing on the role of invasion-associated proteins. MATERIALS AND METHODS: Differentiated thyroid carcinoma cell lines FTC- 133 and XTC.UC1, and anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with alltrans- RA (ATRA) or the solvent ethanol. Invasion and adhesion potency in vitro was studied by transwell experiment and short-term adhesion assay. The involvement of invasion-associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase-2 (MMP-2) and E-cadherin, were investigated by semi-quantitative RT-PCR and Western blot. RESULTS: In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines, with the most significant effect in anaplastic cancer cells. Short-term adhesion assay suggested that ATRA increases cancer cell adhesion to extracellular matrix (ECM) in C643, HTH74 and XTC.UC1, probably through a transcriptional and translational regulation of some attachment molecules. RT-PCR andWestern blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-cadherin was increased, whereas the MMP-2 expression was not significantly down-regulated in ATRA-treated group. In ATRA-treated FTC-133 and XTC.UC1 cell lines, MMP-2 expression was decreased, but no significant changes in uPA and E-cadherin expression were observed. CONCLUSIONS: The present study demonstrates the influence of ATRA on both important determinants of metastatic behavior ("de-adhesion" and proteolysis) in thyroid carcinoma cell lines, especially in anaplastic cancer cells. These findings may add to the explanations for beneficial effects of RA in the treatment of metastatic thyroid carcinomas.

Downregulation of TrkA expression in primary sensory neurons after unilateral lumbar spinal nerve transection and some rescuing effects of nerve growth factor infusion.

Peripheral nerve injury results in sprouting of sympathetic and sensory nerve terminals around large diameter neurons in the dorsal root ganglia (DRG), but the underlying mechanism is not clear. Current study sought to examine changes of the nerve growth factor (NGF) receptor TrkA in DRG and spinal cord after a spinal nerve transection by an immunohistochemical technique and to investigate effects of NGF on the expression of TrkA protein in the same animal model. In the control rat, TrkA immunoreactivity was localized to about 55 +/ -1% of total neurons in DRG and to laminae I and II of the spinal cord. The percentage of TrkA immunoreactive neurons in DRG and TrkA staining intensity of spinal cord were reduced 1 week after the nerve lesion. The changes became maximal 2 weeks, but recovered partially 4 weeks after the lesion. The size of TrkA immunoreactive neurons dramatically shifted to smaller sizes, becoming more remarkable 4 weeks after the lesion. In the contralateral DRG, the percentage of TrkA immunoreactive neurons also decreased significantly. Exogenous NGF delivered to DRG for 2 weeks partially reversed the reduction of TrkA expression as well as atrophy of TrkA immunoreactive neurons. No TrkA immunoreactive basket was found around neuronal somata. Our data show that unilateral peripheral nerve injury results in dynamic downregulation of TrkA in sensory neurons in bilateral DRG and spinal cord, and that TrkA expression in sensory neurons is partially regulated by target-derived NGF.

A killing disease epidemic among displaced Sudanese population identified as visceral leishmaniasis.

A fatal disease epidemic affected the Bentiu area in southern Sudan and led to a mass migration of the Nuer tribe searching for treatment. The initially available information revealed a high mortality rate due to a possible occurrence of tuberculosis, malaria, enteric fever or visceral leishmaniasis (VL). Serological screening of 53 of the most severely affected patients in an enzyme-linked immunosorbent assay (ELISA) or an improved direct agglutination test (DAT) revealed positivity for VL. In 39 of those patients, diagnosis was confirmed by identification of Leishmania donovani amastigotes in lymph node or bone-marrow aspirates. In a total of 2714 patients observed, 1195 (44.0%) had clinical symptoms suggesting VL: DAT positive titers (1:3200-greater than or equal to 1:12800) were obtained in 654 (24.1%), of whom 325 were confirmed parasitologically. Forty-two VL cases died before or during treatment, giving a mortality rate of 6.4%. Among the intercurrent infections diagnosed in the VL population (654), respiratory involvements (31.7%) and malaria (10.7%) were most prevalent. With the exception of four (0.6%), all other VL patients (509) responded readily to sodium stibogluconate. The factors initiating the outbreak are discussed. Malnutrition and nomadic movements to potential VL endemic areas appeared to be the most important. HIV infection as a possible predisposition seemed remote considering the clinical and epidemiological similarity to VL occurring in East Africa, adequate humoral response in DAT, and immediate positive response to specific anti-Leishmania chemotherapy.