Analysis of the clinical characteristics in 18 patients with novel coronavirus pneumonia: Observational study.

The aim of the present study was to analyze the clinical features, treatments, and short-term prognoses of 18 patients with novel coronavirus pneumonia (NCP) in order to provide reference for further clinical prevention and control of the epidemic. From January 29 to February 29, 2020, data from 18 patients with NCP who were positive for the 2019 novel coronavirus nucleic acid test were collected, and their clinical manifestations, laboratory tests, imaging features, and treatment protocols were analyzed retrospectively. From among the 18 patients with NCP, 9 (50%) were imported cases and 9 (50%) had contact histories with confirmed adult patients. Clinical classification was mainly of the normal type (16 cases, 88.9%). Fever and cough were common clinical symptoms, and the main laboratory indices were lymphocytopenia and leukocytopenia. The main imaging findings yielded ground-glass opacity in 12 cases (66.7%) and patchy opacity in 9 cases (50%). All 18 patients were treated with antiviral therapy and targeted treatment in accordance with their symptoms, returned negative nucleic acid tests (9-23 days) after their treatment, and were cured and discharged by March 5, 2020. During the early stages in Deyang, most patients with NCP were input cases; in the later stages, the main route of infection was close contact within the family. Close contact history in epidemiology, nucleic acid detection, and chest imaging were important references for diagnosis. Antiviral therapy resulted in good therapeutic effects. Adopting multi-departmental consultation and remote consultation in combination with traditional Chinese medicine treatment and psychological counseling may result in a good short-term prognosis.

Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

Autoimmune Disease Associated CLEC16A Variants Convey Risk of Parkinson's Disease in Han Chinese.

CLEC16A is a membrane-associated endosomal protein implicated in regulating autophagy and antigen presentation. Its genetic variants are broadly associated with multiple autoimmune diseases. Parkinson's disease (PD), which undergoes autophagy disruption and neuroinflammation, has been clinically observed, for an extensive amount of time, to be associated with autoimmune diseases. In this study, we aimed to understand whether the autoimmune disease associated CLEC16A variants pleiotropically modulate PD risk. Five of such CLEC16A variants, including rs6498169, rs12708716, rs12917716, rs7200786, and rs2903692, were selected and analyzed in a Han Chinese cohort comprising 515 sporadic PD patients and 504 controls. Results showed that rs6498169 and rs7200786 were significantly associated with PD susceptibility (p = 0.005 and 0.004, respectively; recessive model, p = 0.002 and 0.001, respectively). Rs6498169 was also associated with the PD subtype of postural instability/gait difficulty (p = 0.002). Haplotype analysis showed that the AAG module in order of rs6498169, rs12708716, and rs2903692 was associated with the highest risk for PD (p = 0.0047, OR = 1.42, 95% CI = 1.11-1.82). Functional annotation analyses suggested that rs6498169 had high probability to affect transcription factor binding and target gene expression. In summary, the current study demonstrates that the autoimmune disease associated CLEC16A variants convey risk of PD in Han Chinese. Our findings suggest a pleiotropic role of CLEC16A and strengthen the link between PD and autoimmune diseases.

A Matrigel-based 3D construct of SH-SY5Y cells models the α-synuclein pathologies of Parkinson's disease.

Parkinson's disease (PD) is associated with α-synuclein-based Lewy body pathology, which has been difficult to observe in conventional two-dimensional (2D) cell culture and even in animal models. We herein aimed to develop a three-dimensional (3D) cellular model of PD to recapitulate the α-synuclein pathologies. All-trans-retinoic acid-differentiated human SH-SY5Y cells and Matrigel were optimized for 3D construction. The 3D cultured cells displayed higher tyrosine hydroxylase expression than 2D cells and improved dopaminergic-like phenotypes, as suggested by RNA-sequencing analyses. Multiple forms of α-synuclein, including monomer, and low- and high-molecular mass oligomers, were differentially present in the 2D and 3D cells, but mostly remained unchanged upon N-methyl-4-phenyl pyridine or rotenone treatment. Phosphorylated α-synuclein was accumulated, and detergent-insoluble α-synuclein fraction was observed, in the neurotoxin-treated 3D cells. Importantly, Lewy body-like inclusions were captured in the 3D system, including proteinase K-resistant α-synuclein aggregates, ubiquitin aggregation, and ß-amyloid and ß-sheet protein deposition. The study provides a unique and convenient 3D model of PD that recapitulates critical α-synuclein pathologies and should be useful in multiple PD-associated applications.

CLINICAL APPLICATION OF RT-PCR IN TUBERCULOSIS DNA DETECTION COMBINED WITH TB-IGRA IN THE DIAGNOSIS OF SPUTUM SMEAR-NEGATIVE PULMONARY TUBERCULOSIS.

The aim was to investigate detection of pulmonary alveolar lavage fluid tuberculosis DNA by real-time fluorescent polymerase chain reaction (RT-PCR) combined with clinical application of the sputum smear-negative pulmonary tuberculosis diagnosis with TB interferon-γ release assay (TB-IGRA). From October 2014 to October 2015, 632 outpatients and inpatients treated in our hospital were randomly selected, of which 459 patients as the research group managed with RT-PCR detection combined with TB-IGRA and 173 patients as the control group undergoing electronic bronchoscopy alveolar lavage fluid detection, with detection results statistically evaluated. The positive rate in the research group was 96.51%, i.e. significantly higher than that in the control group (66.47%), yielding a statistically significant difference (χ2=109.68, p=0.00). The true positive rate was 97.7% in the research group and 67.92% in the control group; the true positive rate was significantly higher in the research group patients as compared with the control group, yielding a statistically significant difference (χ2=112.04, p=0.00). The sensitivity and specificity, as well as Youden index were significantly higher in the research group as compared with the control group. In conclusion, TB DNA detection by RT-PCR combined with TB-IGRA is a very good method of diagnosing tuberculosis, and it can be implemented in clinical diagnosis of pulmonary tuberculosis.

LINC01189-miR-586-ZEB1 feedback loop regulates breast cancer progression through Wnt/ß-catenin signaling pathway.

Non-coding RNAs play essential roles in breast cancer progression by regulating proliferation, differentiation, invasion, and metastasis. However, our understanding of most microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in breast cancer is still limited. miR-586 has been identified as an important factor in the progression of some types of cancer, but its exact function and relative regulation mechanisms in breast cancer development need to be further investigated. In this study, we showed miR-586 functioned as an oncogene by promoting breast cancer proliferation and metastasis both in vitro and in vivo. Meanwhile, miR-586 induced Wnt/ß-catenin activation by directly targeting Wnt/ß-catenin signaling antagonists SFRP1 and DKK2/3. Moreover, we demonstrated that LINC01189 functioned as a tumor suppressor and inhibited breast cancer progression through inhibiting an epithelial-mesenchymal transition (EMT)-like phenotype by sponging miR-586. In addition, ß-catenin/TCF4 transactivated ZEB1, resulting in a transcriptional repression of LINC01189 expression. In conclusion, our data uncovered the LINC01189-miR-586-ZEB1 feedback loop and provided a novel mechanism participating in the regulation of Wnt/ß-catenin signaling in breast cancer progression.

The Frequency of Natural Killer Cell Subsets in Patients with Acquired Immune Deficiency Syndrome with Deep Fungal Infections.

OBJECTIVE: This study aimed to investigate the expression of natural killer (NK) cell subsets in patients with acquired immune deficiency syndrome (AIDS) and deep fungal infections and the significance of such expression. METHODS: A total of 829 patients with AIDS, who were treated in People's Hospital of Deyang City our hospital between January 2011 and March 2019, were enrolled in the study. They were divided into two groups: those with human immunodeficiency virus (HIV) and invasive fungal infection (IFI) (HIV + IFI) (n = 390) and those with HIV and no IFI (HIV + non-IFI) (n = 439). Another 200 healthy volunteers were enrolled as the control group. The numbers of NK cell subsets in each group were compared. RESULTS: The level of NK cells, number of NK cells in all lymphocytes, proportions of CD56bright, CD56dim, and CD56dim NK cells in NK cells, and the level of CD56-CD16+ NK cells were significantly lower in the HIV + IFI group than in the HIV + non-IFI group and control group (P < 0.05). Moreover, CD4+ T, CD4+/CD8+, and NK cells were negatively correlated with HIV-RNA expression (P < 0.05). CONCLUSION: A combination of AIDS and deep fungal infection can change the immune status of a patient. This condition can be diagnosed early through the detection of NK cell expression.

The ERα-miR-575-p27 feedback loop regulates tamoxifen sensitivity in ER-positive Breast Cancer.

Background: Breast cancer is the most common malignancy, and approximately 70% of breast cancers are estrogen receptor-α (ERα) positive. The anti-estrogen tamoxifen is a highly effective and commonly used treatment for patients with ER+ breast cancer. However, 30% of breast cancer patients fail adjuvant tamoxifen therapy and most of metastatic breast cancer patients develop tamoxifen resistance. Although increasing evidence suggests that microRNA (miRNA) dysregulation influences tamoxifen sensitivity, the mechanism of the cross-talk between miRNA and ERα signaling remains unclear. miR-575 has been reported to be involved in carcinogenesis and progression, however, the role of miR-575 in breast cancer remains limited. The aim of this study was to understand the mechanism of miR-575 in breast cancer tamoxifen resistance. Method: RT-qPCR was employed to assess miR-575 expression in breast cancer tissues and cell lines. The association of miR-575 expression with overall survival in patients with breast cancer was evaluated with KM plotter. Additionally, the effects of miR-575 on breast cancer proliferation and tamoxifen sensitivity were investigated both in vitro and in vivo. Bioinformatic analyses and luciferase reporter assays were performed to validate CDKN1B and BRCA1 as direct targets of miR-31-5p. The ERα binding sites in the miR-575 promoter region was validated with ChIP and luciferase assays. ERα interactions with CDKN1B, cyclin D1 or BRCA1 were determined by IP analysis, and protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Results: miR-575 levels were higher in ER+ breast cancer than in ER- breast cancer and patients with high miR-575 expression had a significantly poorer outcome than those with low miR-575 expression. ERα bound the miR-575 promoter to activate its transcription, and tamoxifen treatment downregulated miR-575 expression in ER+ breast cancer. Overexpression of miR-575 decreased tamoxifen sensitivity by targeting CDKN1B and BRCA1. CDKN1B and BRCA1 were both able to antagonize ERα activity by inhibiting ERα nuclear translocation and interaction with cyclin D1. Furthermore, miR-575 expression was found to be upregulated in ER+ breast cancer cell with acquired tamoxifen resistance, whereas depletion of miR-575 partially re-sensitized these cells to tamoxifen by regulation of CDKN1B. Conclusions: Our data reveal the ERα-miR-575-CDKN1B feedback loop in ER+ breast cancer, suggesting that miR-575 can be used as a prognostic biomarker in patients with ER+ breast cancer, as well as a predictor or a promising target for tamoxifen sensitivity.